JP4948164B2 - 分娩後由来細胞を用いた軟部組織の修復と再生 - Google Patents
分娩後由来細胞を用いた軟部組織の修復と再生 Download PDFInfo
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Description
本明細書は、2003年6月27日に提出された米国仮出願番号第60/483,26
4号に優先権を主張したものであり、その全内容はこの参照により本明細書に組み込まれ
ている。この出願はまた、2004年6月25日に提出された米国出願番号第10/877,012[ETH−5073 NP1]号、2004年6月25日に提出された米国出願番号第10/877,446[ETH−5073 NP2]号、2004年6月25日に提出された米国出願番号第10/877,269[ETH−5073 NP3]号、2004年6月25日に提出された米国出願番号第10/877,445[ETH−5073 NP4]号、2004年6月25日に提出された米国出願番号第10/877,541[ETH−5073 NP5]号、2004年6月25日に提出された米国出願番号第10/876,998[ETH−5073 NP8]号、2004年3月24日に提出された米国仮出願番号第60/555,908[ETH 5127]号などの同一出願人による同時係属出願に関連し、そのそれぞれの内容全体はこの参照により本明細書に組み込まれている。
本発明は、哺乳類の細胞生物学と細胞培養の分野に関するものである。特に、本発明は軟部組織細胞系譜の細胞を支持し、および/または軟部組織細胞に分化する能力を有する、分娩後組織由来の培養細胞と、調整法およびこれらの分娩後組織由来細胞の利用に関するものである。本発明は、軟部組織の再生と修復で、また軟部組織の疾患に対する細胞を基本とした治療で、そのような分娩後由来細胞を使用する方法に関するものでもある。
GCP−2、組織因子、ビメチン、α−平滑筋アクチンの少なくとも1つの産生と、フローサイトメトリーで検出されるとおり、NOGO−A、GRO−αまたは酸化低密度リポ蛋白質受容体の少なくとも1つの産生がない、少なくとも1つの産生がない場合と、CD10、CD13、CD44、CD73、CD90、PDGFr−α、PD−L2、HLA−A、B、Cの少なくとも1つの産生と、
フローサイトメトリーで検出されるとおり、CD31、CD34、CD45、CD80、CD86、CD117、CD141、CD178、B7−H2、HLA−G、HLA−DR、DP、DQの少なくとも1つの産生がないことと、
線維芽細胞、間葉幹細胞、または回腸稜(iliac crest)骨髄細胞であるヒト細胞と関連した発現が、インターロイキン8、レチキュロン1、ケモカイン(C−X−Cモチーフ)リガンド1(メラノーマ増殖刺激活性、α)、ケモカイン(C−X−Cモチーフ)リガンド6(顆粒球走化性蛋白質2)、ケモカイン(C−X−Cモチーフ)リガンド3、腫瘍壊死因子、α誘導蛋白質3の少なくとも1つで発現が上昇すること、または線維芽細胞、間葉幹細胞、または回腸稜の骨髄細胞であるヒト細胞と関連した発現が、C型レクチンスーパーファミリーメンバーA2、ウィルムス腫瘍1、アルデヒド・デヒドロゲナーゼ1ファミリーメンバーA2、レニン、酸化低密度リポ蛋白質受容体1、蛋白質キナーゼCゼータ、クローンIMAGE:4179671、卵巣癌で下方制御された遺伝子1、仮想蛋白質DKFZp564F013、クローンDKFZp547K1113の少なくとも1つで発現が上昇することと、
線維芽細胞、間葉幹細胞、または回腸稜骨髄細胞であるヒト細胞と関連した発現が、少なくとも以下の1つで減少し、これが低身長感受性ホメオボックス2、熱ショック27kDa蛋白質2、ケモカイン(C−X−Cモチーフ)リガンド12(間質細胞由来因子1)、エラスチン、cDNA DKFZp586M2022(クローンDKFZp586M2022より)、間質系ホメオボックス2、sine oculis ホメオボックスホモログ1、クリスタリン、αB、形態形成のdishevelled関連性活性化因子2、DKFZP586B2420蛋白質、ニューラリン1の類似体、テトラネクチン、srcホモロジー3(SH3)およびシステインリッチドメイン、B−細胞転座遺伝子1、抗増殖性物質、コレステロール25−水酸化酵素、ラント関連転写因子3、仮想蛋白質FLJ23191、インターロイキン11受容体α、プロコラーゲンC−エンドペプチダーゼエンハンサー、縮合(frizzled)相同体7、仮想遺伝子BC008967、コラーゲンVIII型、α1、テネイシンC、イルコイホメオボックスタンパク質5、へファエスチン、インテグリン、β8、シナプス小胞糖タンパク質2、cDNA FLJ12280 fis、クローンMAMMA1001744、サイトカイン受容体様因子1、カリウム中間体/低透過性カルシウム活性化チャネル、サブファミリーN、メンバー4、インテグリン、α7、DKFZP586L151蛋白質、PDZ−結合モチーフ(TAZ)を有する転写コアクチベーター、sine oculis ホメオボックス相同体2、KIAA1034蛋白質、初期成長反応3、ディスタルレス(distal−less)ホメオボックス5、仮想蛋白質FLJ20373、アルド−ケトレダクターゼファミリー1、メンバーC3(3−αヒドロキシステロイド脱水素酵素II型)、ビグリカン、ファブロネクチン1、プロエンケファリン、インテグリン、β様1(EGF様反復ドメインを有する)、cDNAクローンEUROIMAGE 1968422、EphA3、KIAA0367蛋白質、ナトリウム利尿ペプチド受容体C/グアニル酸シクラーゼC(房室ナトリウム利尿ペプチド受容体C)、仮想蛋白質FLJ14054、cDNA DKFZp564B222(クローンDKFZp564B222より)、小胞関連性膜タンパク質5、EGF含有フィブリン様細胞外マトリックスタンパク質1、BCL2/アデノウィルスE1B 19kDa相互作用タンパク質3様;AE結合タンパク質1;シトクロームcオキシダーゼサブユニットVIIaポリペプチド1(筋肉)、線維芽細胞種、腫瘍原性1の抑制、インスリン様増殖因子結合蛋白質2、36kDaである場合と、
MCP−1、IL−6、IL−8、GCP−2、HGF、KGF、FGF、HB−EGF、BDNF、TPO、MIP1a、RANTES、TIMP1の少なくとも1つの分泌と、
ELISAで検出されるTGF−β2、ANG2、PDGFbb、MIP1b、I309、MDC、VEGFの少なくとも1つの分泌がない場合と、
培養で少なくとも40集団倍加を受ける能力の特徴のうち少なくとも1つを有する。
本明細書と請求項で使用される様々な用語は、以下に説明するとおりに定義される。
ANG2(またはAng2)はアンジオポエチン2、
APCは抗原提示細胞、
BDNFは脳由来神経栄養因子、
bFGFは塩基性線維芽細胞増殖因子、
bid(BID)は「1日2回」、
BSPは骨シアロ蛋白質、
CK18はサイトケラチン18、
CXCリガンド3はケモカイン受容体リガンド3、
DAPIは4’−6−ジアミジノ−2−フェニルインドール−2HCl、
DMEMはダルベッコ変法イーグル培地、
DMEM:lg(またはDMEM:Lg、DMEM:LG)はDMEMと低グルコース、
EDTAはエチレンジアミン四酢酸、
EGF(またはE)は上皮増殖因子、
EPOはエリスロポエチン、
FACSは蛍光活性細胞分類
FBSはウシ胎仔血清、
FGF(またはF)は線維芽細胞増殖因子、
GCP−2は顆粒球走化性蛋白質−2、
GDF−5は増殖および分化因子5、
GFAPはグリア線維酸性蛋白質、
HB−EGFはヘパリン結合上皮増殖因子、
HCAECはヒト冠動脈内皮細胞、
HGFは肝細胞増殖因子、
hMSCはヒト間葉幹細胞、
HNF−1αは、肝細胞特異的転写因子、
HUVECはヒト臍静脈内皮細胞、
I309はケモカインであって、前記CCR8受容体に対するリガンドであり、TH2型T細胞の化学親和性の原因である、
IGFはインスリン様増殖因子、
IL−6はインターロイキン−6、
IL−8はインターロイキン8、
K19はケラチン19、
K8はケラチン8、
KGFは角化細胞増殖因子、
MCP−1は単球走化性蛋白質1、
MDCはマクロファージ由来ケモカイン、
MIP1αはマクロファージ炎症性蛋白質1α、
MIP1βはマクロファージ炎症性蛋白質1β、
MMPはマトリックスメタロプロテアーゼ(MMP)、
MSCは間葉幹細胞、
NHDFは正常ヒト皮膚線維芽細胞、
NPEは神経前駆細胞増殖培地、
OxLDLRは酸化低密度リポ蛋白質受容体、
PBMCは末梢血単核球、
PBSはリン酸緩衝生理食塩水、
PDCは胎盤由来細胞、
PDGFbbは血小板由来増殖因子、
PDGFr−αは血小板由来増殖因子受容体α、
PD−L2はプログラム死リガンド2、
PEはフィコエリトイン、
POは「経口」、
PPDCは分娩後由来細胞、
Rantes(またはRANTES)は活性化を調節された、発現および分泌された正常T細胞、
rbはウサギ、
rhは組み換えヒト、
SCは皮下、
SCIDは重度複合免疫不全、
SDF−1αは間質由来因子1α、
SHHはソニック・ヘッジホッグ、
SMAは平滑筋アクチン、
SOPは標準操作手順書、
TARCは胸腺および活性化制御ケモカイン、
TCPは組織培養プラスチック、
TGFβ2はトランスフォーミング増殖因子β2、
TGFβ3はトランスフォーミング増殖因子β3、
TIMP1は組織マトリックスメタロプロテアーゼ阻害物質1、
TPOはトロンボポエチン、
TuJ1はBIIIチューブリン、
UDCは臍帯由来細胞、
VEGFは血管内皮増殖因子、
vWFはフォンウィルブランド因子、
αFPはαフェトプロテインである。
様々な特許および他の刊行物はここで、本明細書中に引用され、それぞれその全体が参考文献に盛り込まれている。
ここで説明された方法によれば、哺乳類の胎盤と臍帯は、満期産または早期産のいずれかの終結点のその直後、例えば出産後の娩出後に回復される。分娩後組織は、経膣的、または他の方法、例えば帝王切開を用いるかによらず、完了した妊娠から満期または満期前のすべてから得られる可能性がある。前記分娩後組織は前記出産施設から実験室に、フラスコ、ビーカー、培養皿、またはバッグなどの無菌容器で輸送されてもよい。前記容器は、これだけに限らないが、例えばダルベッコ変法イーグル培地(DMEM)またはリン酸緩衝生理食塩水(PBS)などの塩溶液を含む溶媒または培地、またはウィスコンシン大学溶液またはペルフルオロ化合物溶液など、移植に使用される臓器の輸送に使用するすべての溶液を有してもよい。これだけに限らないが、ペニシリン、ストレプトマイシン、アンフォテリシンB、ゲンタマイシン、ナイスタチンなど、1若しくはそれ以上の抗生物質および/または抗真菌剤が培地または緩衝液に追加されてもよい。前記分娩後組織は、ヘパリン含有溶液などの抗凝固溶液で洗い流してもよい。PPDCの抽出前に約4〜10℃で前記組織を保持することが好ましい。前記組織はPPDCの抽出前に凍結されないことがさらに好ましい。
PPDCは例えば増殖特性(例えば集団倍加能、倍加時間、老化までの継代)、核型分析(例えば正常な核型、母体または新生児の細胞系譜)、フローサイトメトリー(例えばFACS分析)、免疫組織化学および/または免疫細胞化学(例えばこれだけに限らないが、ビメチン、デスミン、α−平滑筋アクチン、サイトケラチン18、フォン・ヴィルブランド因子、CD34、GROα、GCP−2、酸化低密度リポ蛋白質受容体1、NOGO−Aを含むエピトープの検出)、遺伝子発現プロファイリング(例えば、遺伝子チップアレイ、ポリメラーゼ連鎖反応(例えば、逆転写酵素PCR、リアルタイムPCR、従来のPCR))、蛋白質配列、蛋白質の分泌(例えば、血漿凝固アッセイまたはPPDC条件培地の分析により、例えば、酵素結合免疫吸着検定法(ELISA)による)、抗体分析(例えばELISA、これだけに限らないが、CD10、CD13、CD31、CD34、CD44、CD45、CD73、CD80、CD86、CD90、CD117、CD141、CD178、血小板由来増殖因子受容体α(PDGFr−α)、HLAクラスI抗原(HLA−A、HLA−B、HLA−C)、HLAクラスII抗原(HLA−DP、HLA−DQ、HLA−DR)、B7−H2、PD−L2を含む細胞表面マーカーの抗体染色)、混合リンパ球反応(例えば、同種PBMC刺激の指標として)、および/または他の当該分野に既知の方法で特徴付けられてもよい。
PPDCの遺伝子工学
本発明の前記細胞は設計され、これだけに限らないが、組み込み型ウイルスベクター、例えばレトロウイルスベクターまたはアデノ関連ウイルスベクター、非組み込み型複製ベクター、例えばパピローマウイルスベクター、SV40ベクター、アデノウイルスベクター、または複製欠陥ウイルスベクターを含む様々なベクターのいずれかを利用することができる。細胞にDNAを導入する他の方法には、リポソーム、電気穿孔法、粒子ガムの利用を含み、または直接DNA注入法による。
PPDCによる増殖因子の分泌は、in vitroまたはin vivoで第2の細胞タイプの栄養支持を提供してもよい。PPDCは例えば少なくとも単球走化性蛋白質1(MCP−1)、インターロイキン−6(IL6)、インターロイキン8(IL−8)、GCP−2、肝細胞増殖因子(HGF)、角化細胞増殖因子(KGF)、線維芽細胞増殖因子(FGF)、ヘパリン結合性上皮増殖因子(HB−EGF)、脳由来神経栄養因子(BDNF)、トロンボポエチン(TPO)、マクロファージ炎症性タンパク質1α(MIP1a)、RANTES、組織マトリックスメタロプロテアーゼ阻害物質1(TIMP1)の少なくとも1つを分泌してもよく、化学的に定義された培地における前記細胞のex vivo培養を含め、様々な方法により増殖される可能性がある。
本発明の別の実施例では、特定の細胞系譜に分化を刺激する条件でインキュベートされた未分化PPDCまたはPPDCから、条件培地の産生にPPDCを使用することを特徴としている。そのような条件培地は、例えば幹細胞または軟部組織前駆体細胞、またはこれだけに限らないが、上皮細胞(例えば口腔粘膜、消化管、鼻上皮、気道上皮、膣上皮、角膜上皮の細胞)、骨髄細胞、脂肪細胞、幹細胞、角化細胞、血管内皮細胞(例えば、大動脈内皮細胞、冠動脈内皮細胞、肺動脈内皮細胞、腸骨動脈内皮細胞、微小血管内皮細胞、臍動脈内皮細胞、臍静脈内皮細胞、血管内皮前駆体(例えばCD34+、CD34+/CD117+細胞))、筋芽細胞、筋細胞、間質細胞、その他の軟部組織細胞または前駆細胞、およびその混合物を含む軟部組織表現型の細胞などの細胞のin vitroまたはex vivo培養での使用、またはin vivoでPPDCまたは幹細胞または前駆細胞の均一または不均一な集団、および/または軟部組織表現型の細胞、上皮細胞(例えば口腔粘膜、消化管、鼻上皮、気道上皮、膣上皮、角膜上皮の細胞)、骨髄細胞、脂肪細胞、幹細胞、角化細胞、血管内皮細胞(例えば、大動脈内皮細胞、冠動脈内皮細胞、肺動脈内皮細胞、腸骨動脈内皮細胞、微小血管内皮細胞、臍動脈内皮細胞、臍静脈内皮細胞、血管内皮前駆体(例えばCD34+、CD34+/CD117+細胞))、筋芽細胞、筋細胞、間質細胞、その他の軟部組織細胞または前駆細胞、およびその混合物を有する移植細胞を支持することが意図される。
軟部組織状態を有する患者、例えばこれだけに限らないが、正常に発達するため、疾患または前記組織の外傷または不全の結果生じる軟部組織の修復または置換を必要とする患者を治療するため、または前記身体の機能を増加するなど、美容機能を提供するために本発明のPPDCが用いられてもよく。本発明のPPDCの治療応用は、ヘルニア、前記骨盤底の損傷、腱または靱帯の裂傷または破裂、皮膚の修復および再生(例えば瘢痕の補正または外傷の治療、重度の熱傷、皮膚潰瘍(例えば褥痩性潰瘍(床擦れ)、静脈性潰瘍、糖尿病性潰瘍)、皮膚癌の切除に伴うものなど外科創傷、血管疾患の治療(例えば末梢動脈疾患、腹部大動脈瘤、頸動脈疾患、静脈疾患などの血管疾患、血管外傷、不適切な血管発達)、および筋疾患(例えば先天性ミオパシー、重症筋無力症、炎症性、神経性、筋原性筋疾患、またデュシェンヌ型筋ジストロフィー、ベッカー型筋ジストロフィー、筋強直性ジストロフィー、肢帯筋異栄養症、顔面・肩甲・上腕筋ジストロフィー、先天型筋ジストロフィー、眼球咽頭型筋ジストロフィー、末梢型筋ジストロフィー、エメリー・ドレフュス型筋ジストロフィーなどの筋ジストロフィー)の治療を含むが、これだけに限らない。
例えば薬学的組成物を含む、PPDCと関連製品の組成物(例えば細胞外基質、細胞溶解物、可溶性細胞分画、条件培地)は、本発明の範囲内に含まれる。本発明の組成物には、例えばこれだけに限らないが、増殖因子、分化誘導因子、カスパーゼ阻害薬などの細胞生存因子、p38キナーゼ阻害薬などの抗炎症性因子、またはVEGFまたはbFGFなどの血管新生因子など、1若しくはそれ以上の生理活性因子を含んでもよい。生理活性因子のいくつかの例には、PDGF−bb、EGF、bFGF、IGF−1、LIFを含む。いくつかの実施例では、未分化または分化誘導PDPCが前記生理活性因子と接触して培養される。いくつかの実施例では、未分化PPDCが前記生理活性因子と接触した時点でまだ未分化である。他の実施例では、生理活性因子が前記PPDCの分化を誘導する。例えば薬学的組成物を含む、PPDCと関連製品の組成物(例えば細胞外基質、細胞溶解物、可溶性細胞分画、条件培地)は、本発明の範囲内に含まれる。本発明の組成物には、1若しくはそれ以上の分化誘導因子、カスパーゼ阻害薬などの細胞生存因子、p38キナーゼ阻害薬などの抗炎症性因子、またはVEGFまたはbFGFなどの血管新生因子を含んでもよい。
本題の発明の治療法には、それを必要とする患者にPPDC、PPDC製剤、またはトランス分化した細胞の移植が関与する。本発明の細胞は、治療が必要な部位または前記部位の「ホーム」に送達されてもよい。
限定しない実施例では、本発明の前記細胞を有する製剤が、新規軟部組織の産生が望ましい部位に直接投与するために調整される。例えば、限定されないが、本発明の前記細胞は注射用ヒドロゲル溶液で懸濁されてもよい。本発明で使用されるために適切なヒドロゲルの例には、RAD16などの自己集合性ペプチドを含む。代わりに、前記細胞を含むヒドロゲル溶液は、例えば鋳型に固めることができ、移植前にそこに分散される細胞を有する基質を形成してもよい。または一度前記基質が固まると、前記細胞が移植前に有糸分裂により増殖されるように、前記細胞構造が培養されてもよい。前記ヒドロゲルは、共有、イオン、または水素結合を介して交差結合され、水分子を包括してゲルを形成する三次元開放型格子構造を形成する、有機ポリマー(天然型または合成型)である。ヒドロゲルを形成するために用いられる可能性がある物質の例には、アルギン酸とその塩、ペプチド、ポリホスファジン、ポリアクリル酸塩などの多糖類を含み、イオンにより架橋されるか、ポリエチレン・オキシド−ポリプロピレングリコールブロックコポリマーなどのポリマーを遮断し、それぞれ温度またはpHにより架橋される。いくつかの実施例では、本発明のPPDCの支持体が生物分解性である。
事前に形成されたウェルでのPPDCの培養または共培養は、事前に定められた厚さと容積の軟部組織パッチの製造を可能とする。前記で得られた組織パッチの容積は、前記ウェルの容積と前記ウェル中のPPDC数に依存する。最適な事前に決定された容積の組織は、前記パラメーターのいずれかまたは両方を変化させることで、日常的な実験により調整されてもよい。
いくつかの実施例では、PPDCが利用され、細胞シートを生成する。前記シートはShimizu,et al.,Biomaterials,24(13):2309〜2316(2003)で説明されるとおり、多層としてもよい。
本発明またはその共培養の細胞は、三次元骨格に播種され、in vivoで移植されてもよく、前記播種細胞は前記骨格で増殖し、前記患者の細胞と協力してin vivoで置換組織を形成する。
PPDCは平面骨格に播種される可能性がある。前記骨格は好ましくは移植前に培地に播種される。2若しくはそれ以上の平面骨格が別に上に置かれ、一緒に縫合されて多層骨格を形成する可能性がある。
例えば、これだけに限らないが、前記三次元骨格が利用され、in vitroで単一および多層の管状組織を構築し、これはin vivoで障害を受けたか、疾患のある管状組織の置換とすることができる。
以下の小区分は、播種された骨格を利用し、前記身体に移植されうるチューブを調整する方法を説明している。
前記幅が前記管状臓器の内周にほぼ等しく、最終的に管状組織に挿入される細長い一片(例えば、長方形)に骨格が切断されうる。液体培地に浮遊させ、懸濁されることで、前記細胞が前記骨格に播種され、インキュベートされうる。適切なコンフルエントの段階で、長い方の端をつなぐことで、前記骨格がチューブに囲まれてもよい。前記縫い目が、適切な直径で、適切な物質の繊維により2つの端を一緒に縫合することで閉じられてもよい。
本発明に沿って、骨格が管として形成され、PPDCで播種され、培養チャンバーで培地に懸濁されうる。細胞の前記管腔を閉塞させないようにするため、前記管状骨格の開口端の1つがノズルに添付されうる。液体培地が前記インキュベーションチャンバーに接続された供給チャンバーから、このノズルを介して推し進められ、前記管状骨格の内部から電流を作ることができる。前記他の開口端は流出開口部に添付され、これが回収チャンバーにつながり、前記培地が前記供給チャンバーから再循環される可能性がある。インキュベーションが終わると、前記管が前記ノズルと流出開口部から分離されうる。この方法はBallermann,B.J.,et al.、国際出願番号第WO 94/25584号および米国特許第5,843,781号で説明され、そのいずれもその全体がこの参照によってここに盛り込まれている。
一般に、以下の方法のいずれかを用いて本発明により、2つの三次元骨格が管に組み合わされてもよい。
2若しくはそれ以上の平面骨格が別に上に置かれ、一緒に縫合されうる。次にこの2層シートが囲まれ、以下に示すとおり、一緒に接合され、縫合されうる。
前記内層とされる1つの管状骨格がPPDCで播種され、インキュベートされうる。第2の骨格は、前記管状骨格の外周よりもわずかに大きな幅で、平面状の細長い一片として増殖されうる。適切な増殖が得られた後、前記平面骨格が前記管状骨格の外周に巻かれ、次に前記平面骨格の2つの端の継ぎ目を閉じ、好ましくは前記内管に前記平面骨格を固定する。
わずかに異なる直径を持つ、2若しくはそれ以上の管状網が別に増殖されうる。前記より小さな直径を持つ骨格がより大きな直径の骨格に挿入され、固定されうる。
前記管状作成物の内腔面は、前記管状骨格の非血管新生性の内腔表面を与える物質から成り、またはそれにより治療されうる。これらの治療と物質は、内皮増殖、移動、細胞外基質の堆積を促し、維持してもよい。これらの物質と治療の例は、これだけに限らないが、ラミニンとIV型コラーゲンなどの基底膜タンパク質、ePTFEなどの合成物質、PURSPAN(The Polymer Technology Group,Inc.、カリフォルニア州バークリー)などのセグメント化ポリウレタンウレアシリコンなどの天然物質を含む。これらの物質がさらに投与され、前記管状骨格の非血栓形成性の内腔表面を与えることができる。そのような治療は、ヘパリンなどの抗血栓薬、血漿コーティングなどの前記物質の表面荷電を変化させる治療を含む。
最新式バイオリアクターは、機能的骨格組織のin vitro工学の複合要件を満たすために重要である。例えば、強化された環境と流体制御と同時に、三次元基質に対する複合同時機械ひずみを適用する能力を持ったバイオリアクター系が、Altman et al.,J.Biomech.Eng.,124(6):742〜749(2002)、米国特許公開番号第2002/0062151号により提供されている。例えばこれだけに限らないが、バイオリアクターシステムなどが組織工学的腱または靱帯、例えば前十字靱帯の開発で利用されてもよい。
本発明の前記細胞を移植する、またはそこから産生される生組織の代わりとして、組織修復、置換、または増殖を必要とする被験者に、前記細胞外基質(ECM)またはこれらの細胞によって産生される細胞溶解物など、PPDCの成分または産生物の投与から利益が生じてもよい。
本発明の細胞と組織はin vitroで利用され、薬学的組成物の効果と細胞毒性、増殖/制御因子、抗炎症薬について、広範な化合物をスクリーニングしてもよい。このため、本発明の細胞、または前記組織培養はin vitroで管理され、検査すべき化合物に曝露される。細胞毒性化合物の活性は、培養で細胞を障害または死滅させる能力により測定されうる。これは重要な染色法により容易に評価されうる。増殖/制御因子の効果は、in vitroの生細胞数を分析することにより、例えば細胞総量と異なる細胞数により評価されうる。これは、タイプ特異的な細胞抗原を定義する抗体を利用した免疫細胞化学的方法を利用するなど、標準的な細胞学的および/または組織学的方法を用いて達成されてもよい。懸濁培養または前述の三次元系における、本発明の細胞に対する様々な薬物の効果が取り上げられてもよい。
さらなる実施例では、本発明の細胞がin vitroで培養され、高収率で生物学的製剤を産生することができる。例えば、そのような細胞は、特定の対象生物学的製剤(例えば増殖因子、制御因子、またはペプチドホルモン)を自然に産生するか、または生物学的製剤を産生するため遺伝子操作され、例えば上述の三次元培養系を用いてクローン技術により増殖することができる。前記細胞が前記栄養培地に生物学的製剤を分泌する場合、前記製剤が前記使用済みまたは条件培地から、異なるタンパク質沈殿、イオン交換クロマトグラフィー、ゲルろ過クロマトグラフィー、電気泳動、高性能液体クロマトグラフィーなどの標準的な分離法を利用し、容易に単離されうる。「バイオリアクター」は、例えばin vitro三次元培養など、栄養補給を行うための流出法を活用するために利用されうる。
前記PPDCとその成分および製剤は、例えば培養または移植用キットの一部として好都合に利用されうる。従って、本発明は前記PPDCと、基質(例えば骨格)、水和剤(例えば、生理的に適合する食塩水、調整細胞培地)、細胞培養基質(例えば、培養皿、シャーレ、バイアルなど)、細胞培地(液体または粉末形)、抗生物質、ホルモンなどの追加成分を含むキットを提供する。前記キットはそのような成分のいずれかを含むが、好ましくはその意図した使用に必要なすべての成分を含む。望ましい場合は、前記キットが(典型的には凍結保存された)細胞を含む可能性があり、ここで述べられているとおり、前記格子に播種される可能性がある。
本発明のPDCは凍結保存され、「細胞バンク」に維持または保存されてもよい。本発明の細胞の凍結保存は、既知の方法に沿って実行されうる。例えばこれだけに限らないが、5〜10%のグリセロールがある場合とない場合で、例えば約0.5〜10×106個/ミリリットルの密度で、例えばさらに0〜95%のFBS、0〜10%のジメチルスルホキシド(DMSO)を有する培地など、「凍結培地」で細胞が懸濁されてもよい。前記凍結保存培地は、これだけに限らないがメチルセルロースを含む凍結保存剤を有してもよい。前記細胞は、次に制御された比率の冷凍庫に密閉および移動された、ガラスまたはプラスチックアンプルに分配される。最適な冷凍率は経験的に決定されてもよい。例えばプログラム可能な比率の冷凍庫は、毎分−1〜−10℃の温度で変化させることができる。前記好ましい凍結保存温度は約−80℃〜約−180℃であり、さらに好ましくは約−90℃〜約−160℃、最も好ましくは約−125〜約−140℃である。凍結保存された細胞は、使用のために解凍する前に、好ましくは液体窒素に移動される。いくつかの実施例では、例えばアンプルが約−90℃に達した後、液体窒素の保存域に移動される。凍結保存された細胞は数年間保存されうる。
本研究の目的は、胎盤および臍帯組織の細胞集団に由来するものであった。満期または早期妊娠いずれかの出産で、分娩後臍帯および胎盤が入手された。細胞は、臍帯および胎盤組織の5種類のドナーから採取された。1)異なる表現型の細胞に分化する能力、または2)他の細胞および組織に対して有用な、重大な栄養因子を提供する能力がある細胞を得る能力について、様々な細胞単離法が検討された。
臍帯細胞の誘導:臍帯は国立疾病研究互助組織(National Disease Research Interchange、NDRI、ペンシルバニア州フィラデルフィア)から入手された。前記組織は正常出産後に入手された。前記細胞単離プロトコールは、流出フードで無菌的に実行された。血液と壊死組織片を除去するため、前記臍帯が抗真菌剤および抗生物質(100ユニット/ミリリットルのペニシリン、100マイクログラム/ミリリットルのストレプトマイシン、0.25マイクログラム/ミリリットルのアンフォテリシンB)(Invitrogen、カリフォルニア州カールズバッド))存在下、リン酸緩衝生理食塩水(PBS;Invitrogen、カリフォルニア州カールズバッド)で洗浄された。50ミリリットルの培地(DMEM低グルコースまたはDMEM高グルコース、Invitrogen)の存在下、前記組織が細いパルプに切断されるまで、それから前記組織は150cm2の組織培養皿で機械的に分離された。前記細かく切断された組織は、50ミリリットルのチューブ(1本当たり約5グラムの組織)に移動された。前記組織は、次に抗真菌剤と抗生物質(100ユニット/ミリリットルのペニシリン、100マイクログラム/ミリリットルのストレプトマイシン、0.25マイクログラム/ミリリットルのアンフォテリシンB(Invitrogen))および消化酵素をそれぞれ含むDMEM低グルコース培地またはDMEM高グルコース培地で、消化された。いくつかの実験では、コラゲナーゼとディスパーゼの酵素混合物が使用された(「C:D」、DMEM低グルコース培地中、コラゲナーゼ(Sigma、ミズーリー州セントルイス)、500ユニット/ミリリットル、ディスパーゼ(Invitrogen)、50ユニット/ミリリットル)。他の実験では、コラゲナーゼ、ディスパーゼ、ヒアルロニダーゼの混合物(「C:D:H」)が使用された(DMEM低グルコース中コラゲナーゼ500ユニット/ミリリットル、ディスパーゼ50ユニット/ミリリットル、ヒアルロニダーゼ(Sigma)、5ユニット/ミリリットル)。前記組織、培地、消化酵素を含むコニカルチューブが、37℃、環状シェーカー(Environ、ニューヨーク州ブルックリン)で、225rpm、2時間インキュベートされた。
異なる酵素の組み合わせを用いた細胞単離:C:D:Hの組み合わせが単離後の最高細胞収率を提供し、前記他の条件よりも培養でより多くの世代を拡大させた細胞を生成した(表1−1)。増殖可能な細胞集団は、コラゲナーゼまたはヒアルロニダーゼのみを用いて達成されなかった。この結果が検討された前記コラーゲンに特異的であるか否かを決定する試みは行われなかった。
1.HO,Tony,W.;KOPEN,Gene,C.;RIGHTER,William,F.;RUTKOWSKI,J.,Lynn;HERRING,W.,Joseph;RAGAGLIA,Vanessa;WAGNER,Joseph 国際公開公報第WO2003025149 A2号 CELL POLULATIONS WHICH CO−EXPRESS CD49C AND CD90,NEURONYX,INC.国際出願番号第PCT/US02/29971号、2002年9月20日出願、2003年3月27日A2公開、2003年12月18日A3公開。
いくつかの細胞培地で、胎盤由来細胞の増殖を支持する能力が評価された。正常(20%)および低(5%)酸素状態での胎盤由来細胞の増殖は、前記MTS比色測定法を用いて3日後に評価された。
継代8(P8)における胎盤由来細胞は、増殖培地(DMEM−低グルコース(Gibco、カリフォルニア州カールズバッド)、15%(v/v)ウシ胎仔血清(Cat.#SH30070.03、Hyclone、ユタ州ローガン)、0.001%(v/v)ベータメルカプトエタノール(Sigma、ミズーリー州セントルイス)、50ユニット/ミリリットルのペニシリン、50マイクログラム/ミリリットルのストレプトマイシン(Gibco))中、96ウェルのプレート、1×103細胞/ウェルで播種された。8時間後、表2−1で説明されたとおりに前記培地が変化され、細胞は37℃、5% CO2で48時間、正常(20%、v/v)または低(5%、v/v)酸素状態でインキュベートされた。MTSは3時間前記培地(CELLTITER 96 Aqueous一溶液細胞増殖アッセイ、Promega、ウィスコンシン州マディソン)に追加され、前記吸光度は490ナノメーターで測定された(Molecular Devices、カリフォルニア州サニーベール)。
前記MTSアッセイの標準曲線は、吸光度の上昇と細胞数の上昇の間で線形相関を確立した。得られた吸光度の値は推定細胞数に変換され、前記最初の播種に対する変化(%)が計算された。
通常のL−バリンイソ型の代わりにD−バリンを含む培地が利用され、培地で線維芽細胞様の細胞増殖を選択的に抑制させることが報告された(Hongpaisan、2000;Sordilloら、1988)。L−バリンがない状態でD−バリンを含む培地において、分娩後由来細胞の増殖が評価された。
ゼラチンでコーティングしたT75フラスコ中、5×103細胞/cm2で胎盤由来細胞(P3)、線維芽細胞(P9)、臍帯由来細胞(P5)が播種された(Corning、ニューヨーク州コーニング)。24時間後、前記培地が除去され、前記細胞がリン酸緩衝生理食塩水(PBS)(Gibco、ニューヨーク州コーニング)で洗い流され、残りの培地を除去した。前記培地が修正増殖培地(D−バリン(特注、Gibco)、15%(v/v)透析ウシ胎児血清(Hyclone、ユタ州ローガン)、0.001%(v/v)ベータメルカプトエタノール(Sigma)、50ユニット/ミリリットルのペニシリン、50マイクログラム/ミリリットルのストレプトマイシン(Gibco)を用いたDMEM)で置換された。
透析された血清を含む増殖培地に播種された細胞と異なり、D−バリン含有培地に播種される胎盤由来細胞、臍帯由来細胞、線維芽細胞は増殖しなかった。線維芽細胞は形態学的に変化し、サイズが増加し、形が変化した。前記細胞のすべてが死滅し、最終的に4週間後、フラスコ表面から剥離した。
Hongpaisan J.(2000)Inhibition of proliferation of contaminating fibroblasts by D−valine in cultures of smooth muscle cells from human myometrium.Cell Biol Int.24:1〜7.
Sordillo LM,Oliver SP,Akers RM.(1988)Culture of bovine mammary epithelial cells in D−valine modified medium: selective removal of contaminating fibroblasts.Cell Biol Int Rep.12:355〜64.
本研究の目的は、分娩後由来細胞の凍結保存用に適切な凍結保存培地を決定することであった。
ゼラチンでコーティングされたT75フラスコ中、増殖培地(DMEM−低グルコース(Gibco、カリフォルニア州カールズバッド)、15%(v/v)ウシ胎仔血清(Cat.#SH30070.03、Hyclone、ユタ州ローガン)、0.001%(v/v)ベータメルカプトエタノール(Sigma、ミズーリー州セントルイス)、50ユニット/ミリリットルのペニシリン、50マイクログラム/ミリリットルのストレプトマイシン(Gibco))で増殖された分娩後由来細胞は、リン酸緩衝生理食塩水(PBS;Gibco)で洗浄され、1ミリリットルのトリプシン/EDTA(Gibco)を用いてトリプシン処理された。前記トリプシン処理は10ミリリットルの増殖培地を追加することで停止された。前記細胞は150xgで遠心分離され、上清が除去され、前記細胞ペレットは1ミリリットルの増殖培地に再懸濁された。一定分量の細胞懸濁液60マイクロリットルが除去され、60マイクロリットルのトリパンブルー(Sigma)に追加された。血球計数板を用い、前記生存能力のある細胞数が推定された。前記細胞懸濁液がそれぞれ88×104細胞を含む4等分量に分割された。前記細胞懸濁液が各培地1ミリリットル未満に遠心分離、再懸濁され、Cryovials(Nalgene)に移された。
2.)細胞凍結培地w/DMSO、w/メチルセルロース、血清なし(C6295、Sigma、ミズーリー州セントルイス)
3.)細胞凍結培地、血清なし(C2639、Sigma、ミズーリー州セントルイス)
4.)細胞凍結培地、w/グリセロール(C6039、Sigma、ミズーリー州セントルイス)
凍結乾燥される前記細胞の最初の生存可能性は、トリパンブルー染色で100%と評価された。
単離された幹細胞の他の集団と、分娩後由来細胞の細胞増殖の可能性が比較された。老化に対する細胞増殖の方法は、Hayflickの限度として引用される(Hayflick L.The longevity of cultured human cells.J.Am.Geriatr.Soc.22(1):1〜12,1974;Hayflick L.The strategy of senescence.Gerontologist 14(1):37〜45),1974)。十分な細胞数に容易に増殖されうるため、分娩後由来細胞は治療用として非常に適している。
ゼラチンコーティングフラスコ:組織培養プラスチック製フラスコは、室温で20分間、20ミリリットルの2%(w/v)ブタゼラチン(Type B: 225 Bloom;Sigma、ミズーリー州セントルイス)をT75フラスコ(Corning、ニューヨーク州コーニング)に追加することでコーティングされた。前記ゼラチン溶液を除去した後、10ミリリットルのリン酸緩衝生理食塩水(PBS)(Invitrogen、カリフォルニア州カールズバッド)が追加され、次に吸引された。
分娩後由来細胞の増殖の能力と他の幹細胞および非幹細胞集団の比較:臍帯由来および胎盤由来細胞のいずれも、40継代以上増殖し、60日間で細胞収率が>1E17細胞となった。対照的に、MSCと線維芽細胞はそれぞれ25日未満、60日未満後に老化した。脂肪由来および大網細胞のいずれもほぼ60日間増殖したが、これらの細胞の総細胞収率はそれぞれ4.5E12および4.24E13となった。したがって、利用される前記実験条件下、5,000細胞/cm2で播種された場合、分娩後由来細胞は同じ条件で増殖される他の細胞タイプよりもはるかに増殖した(表5−1)。
1)Hayflick L.The longevity of cultured human cells.J Am Geriatr Soc.1974 Jan;22(1):1〜12
2)Hayflick L.The strategy of senescence.Gerontologist.1974 Feb;14(1):37〜45
3)米国特許第20040058412号
4)米国特許第20040048372号
6)Csete,Marie;(Ann Arbor,MI);Doyle,John;(South Pasadena,CA);Wold,Barbara J.;(San Marino,CA);McKay,Ron;(Bethesda,MD);Studer,Lorenz;(New York,NY).Low oxygen culturing of central nervous system progenitor cells.米国特許第20040005704号
細胞療法で利用される細胞系は好ましくは均一であり、汚染細胞タイプはない。細胞療法で利用されるヒト細胞は、正常な染色体数(46)と構造を有する必要がある。均一で非分娩後組織由来の分娩後由来胎盤および臍帯細胞系を同定するため、細胞サンプルの核型が分析された。
男性新生児の分娩後組織のPPDCは、増殖培地(DMEM−低グルコース(Gibco、カリフォルニア州カールズバッド)、15%(v/v)ウシ胎仔血清(FBS)(Hyclone、ユタ州ローガン)、0.001%(v/v)ベータメルカプトエタノール(Sigma、ミズーリー州セントルイス)、50ユニット/ミリリットルのペニシリン、50マイクログラム/ミリリットルのストレプトマイシン(Gibco、カリフォルニア州カールズバッド))で培養された。男性新生児(X,Y)の分娩後組織は、新生児由来細胞と母体由来細胞(X,X)を区別できるように選択された。細胞はT25フラスコ(Corning、ニューヨーク州コーニング)で増殖培地に5,000細胞/平方センチメートルで播種され、約80%コンフルエントに増殖された。細胞を含むT25フラスコは、増殖培地でくびまで充填された。サンプルは宅配業者によって臨床細胞遺伝学研究室に配達された(研究室から研究室への推定移動時間は1時間)。染色体分析は、ニュージャージー州ニューヨーク、New Jersey Medical SchoolのCenter for Human & Molecular Geneticsによって実施された。前記染色体は最も可視化される有糸分裂中期で細胞が分析された。計数された中期の20個の細胞のうち、5個で正常な均一核型数(2)が分析された。2個の核型が観察された場合、細胞サンプルは均一なものとして特徴付けられた。2個以上の核型が観察された場合、細胞サンプルは不均一なものとして特徴付けられた。不均一な核型数(4)が同定されると、追加中期細胞数が計数、分析された。
染色体分析に送られたすべての細胞サンプルは、細胞遺伝学研究室のスタッフにより正常な形態を示すと解釈された。分析された細胞系16種類のうち3種類は均一な表現型を示し(XXおよびXY)、新生児および母体由来の細胞の存在を示した(表6−1)。組織胎盤−N由来の細胞は、胎盤の新生児側から単離された。継代0では、この細胞系がXYで均一であるように見えた。しかし、継代9では、細胞系が不均一であり(XX/XY)、母体由来細胞でこれまで未検出の細胞の存在を示している。
フローサイトメトリーによる細胞表面タンパク質または「マーカー」の特徴は、細胞系の同定を決定するために利用されうる。発現の一貫性は複数のドナーから、異なる処理と培養条件に曝露された細胞で決定される可能性がある。前記胎盤および臍帯から単離した分娩後由来細胞系はフローサイトメトリーで特徴付けられ、それにより本発明の前記細胞を同定するため、プロフィールを提供した。
培地。15%(v/v)ウシ胎仔血清(FBS)(Hyclone、ユタ州ローガン)、0.001%(v/v)ベータメルカプトエタノール(Sigma、ミズーリー州セントルイス)、50ユニット/ミリリットルのペニシリン、50マイクログラム/ミリリットルのストレプトマイシン(Gibco、カリフォルニア州カールズバッド)を含むDMEM低グルコースの増殖培地(Gibco、カリフォルニア州カールズバッド)で細胞が培養された。
胎盤由来細胞は臍帯由来細胞と比較された。CD10、CD13、CD44、CD73、CD90、PDGFr−α、HLA−A、B、Cの産生で陽性であることが示されたフローサイトメトリーで分析された胎盤および臍帯由来細胞は、前記IgGコントロールに対する蛍光値が上昇することで示された。これらの細胞はCD31、CD34、CD45、CD117、CD141、HLA−DR、DP、DQの検出可能な産生が陰性であり、前記IgGコントロールと比較可能な蛍光値が示された。陽性曲線の蛍光値の変化が説明された。前記陽性曲線の平均(つまりCD13)と範囲(つまりCD90)はやや変化を示したが、前記曲線は正常に見え、均一な集団であることが確認された。いずれの曲線も、それぞれIgGコントロール以上の値を示した。
Affymetrix GeneChip(登録商標)アレイが使用され、臍帯と胎盤由来細胞の遺伝子発現プロフィールをヒト骨髄由来の線維芽細胞、ヒト間質幹細胞、別の細胞系と比較した。この分析では前記分娩後由来細胞の特徴を提供し、これらの細胞に独特の分子マーカーを同定した。
細胞の単離と培養
分娩後組織由来細胞:ヒトの臍帯と胎盤は、患者の同意を得て、正常な満期出産において国立疾病研究互助組織(NDRI、ペンシルバニア州フィラデルフィア)から得られた。例1で説明されたとおり、前記組織が受理され、細胞が単離された。ゼラチンコーティングされた組織培養プラスチックフラスコにおいて、増殖培地(15%(v/v)ウシ胎仔血清(Hyclone、ユタ州ローガン)、100ユニット/ミリリットルのペニシリン、100マイクログラム/ミリリットルのストレプトマイシン(Invitrogen、カリフォルニア州カールズバッド)、0.001%(v/v)2−メルカプトエタノール(Sigma、ミズーリー州セントルイス)を用いたダルベッコ変法の基本培地(DMEM低グルコース、Invitrogen、カリフォルニア州カールズバッド))で細胞が培養された。標準的な大気で前記培養が37℃でインキュベートされた。
この研究では、14種類の異なる細胞集団が分析された。継代情報、培養基質、培地に沿った細胞は表8−1に掲載された。
Lockhart et al.,Expression monitoring by hybridization to high−density oligonucleotide arrays.Nat.Biotechnol.1996,14(13):1675〜1680.
前記ヒト胎盤と前記ヒト臍帯に由来する細胞の類似性と違いは、(Affymetrix GENECHIPアレイを用い、)その遺伝子発現プロフィールと他の供給源由来の細胞を比較することで評価された。同定された6種類の「シグネチャー」遺伝子は、酸化LDL受容体1、インターロイキン−8、レニン、レチキュロン、ケモカイン受容体リガンド3(CXCリガンド3)、顆粒球走化性タンパク質2(GCP−2)であった。これらの「シグネチャー」遺伝子は、分娩後由来細胞で比較的高レベルで発現された。
細胞:胎盤由来細胞(核型分析により同定されるとおり、主に新生児の1種類の分離菌を含む3種類の単離株)、臍帯由来細胞(4種類の単離株)、正常ヒト皮膚線維芽細胞(NHDF、新生児および成人)が、ゼラチンでコーティングされたT75フラスコの増殖培地(DMEM−低グルコース(Gibco、カリフォルニア州カールズバッド)、15%(v/v)ウシ胎仔血清(Cat.#SH30070.03;Hyclone、ユタ州ローガン)、0.001%(v/v)ベータ−メルカプトエタノール(Sigma、ミズーリー州セントルイス)、50ユニット/ミリリットルのペニシリン、50マイクログラム/ミリリットルのストレプトマイシン(Gibco、カリフォルニア州カールズバッド)で増殖された。間葉幹細胞(MSC)は、間葉幹細胞の増殖培地一括キット(MSCGM;Cambrex、メリーランド州ウォーカーズビル)で増殖された。
ヒト胎盤由来細胞のcDNA、成人および新生児の線維芽細胞、間葉幹細胞(MSC)について実施された選択された「シグネチャー」遺伝子のリアルタイムPCRの結果は、他の細胞と比べ、前記胎盤由来細胞が高レベルで、酸化LDL受容体およびレニンが発現されたことを示している。リアルタイムPCRから得られたデータは、前記ΔΔCT法によって分析され、対数スケールで表現された。レチキュロンと酸化LDL受容体の発現レベルは、他の細胞と比べて臍帯由来細胞で高かった。分娩後由来細胞と対照では、CXCリガンド3とGCP−2の発現レベルに有意な差は認められなかった(データは示されていない)。CXC−リガンド3は非常に低レベルで発現された。GCP−2はヒト成人および新生児の線維芽細胞と同等のレベルで発現された。リアルタイムPCRの結果は従来のPCRで確認された。PCR製品の配列決定は、さらにこれらの観察の妥当性を確認した。表9−1に掲載された従来のPCR CXCリガンド3プライマーを用い、分娩後由来細胞と対照との間でCXCリガンド3の発現レベルに有意な差は認められなかった。
。
ヒト分娩後組織、つまり臍帯と胎盤内に認められる細胞の表現型は、免疫組織化学的に分析された。
組織標本:ヒト臍帯および胎盤組織が採取され、4%(w/v)パラホルムアルデヒド中、一晩4℃で浸漬固定された。ビメンチン(1:500、Sigma、ミズーリー州セントルイス)、デスミン(1:150、ウサギに対して作成、Sigma、または1:300、マウスに対して作成、Chemicon、カリフォルニア州テメキュラ)、α−平滑筋アクチン(SMA;1:400;Sigma)、サイトケラチン18(CK18;1:400;Sigma)、フォン・ヴィルブランド因子(vWF;1:200;Sigma)、CD34(ヒトCD34クラスIII;1:100;DAKOCytomation、カリフォルニア州カーピンテリア)のエピトープに対する抗体を用い、免疫組織化学検査が実施された。さらに、抗ヒトGROα−PE(1:100;Becton Dickinson、ニュージャージー州フランクリンレイクス)、抗ヒトGCP−2(1:100;anta Cruz Biotech、カリフォルニア州サンタクルーズ)、抗ヒト酸化LDL受容体1(ox−LDL R1;1:100;Santa Cruz Biotech)、抗ヒトNOGA−A(1:100;Santa Cruz,Biotech)のマーカーが検討された。固定された標本が外科用メスで切り取られ、エタノールを含むドライアイス浴でOCT包埋化合物(Tissue−Tek OCT;Sakura、カリフォルニア州トランス)内に入れられた。次に標準的な低温保持装置(Leica Microsystems)を用い、冷凍ブロックが切片にされ(厚さ10ミクロン)、染色用ガラススライドに載せられた。
臍帯の特徴。ビメンチン、デスミン、SMA、CK18、vWF、CD34マーカーは、臍帯に認められる細胞のサブセットで表現された(データは示されていない)。特に、vWFとCD34の発現は前記臍帯内に含まれる血管に制限された。CD34+細胞は最内の層(内腔側)にあった。ビメンチンの発現は、前記臍帯の基質と血管から認められた。SMAは前記動脈および静脈の基質と外壁に限定されていたが、それ自体は前記血管に含まれなかった。CK18とデスミンは前記血管内のみに観察され、デスミンは前記中間層と外層に限定されていた。
細胞培養:2%ゼラチン(Sigma、ミズーリー州セントルイス)でコーティングしたT75フラスコ(Corning、ニューヨーク州コーニング)で、コンフルエントまで増殖培地(DMEM低グルコース(Gibco、カリフォルニア州カールズバッド)、15%(v/v)ウシ胎仔血清(FBS)(Hyclone、ユタ州ローガン)、0.001%(v/v)ベータメルカプトエタノール(Sigma、ミズーリー州セントルイス)、50ユニット/ミリリットルのペニシリン、50マイクログラム/ミリリットルのストレプトマイシン(Gibco、カリフォルニア州カールズバッド))で細胞が培養された。
混合リンパ球反応−胎盤:7種類のヒトボランティア血液ドナーがスクリーニングされ、他の6種類の血液ドナーを用いた混合リンパ球反応において、強固な増殖反応を示す単一の同種ドナーを同定した。このドナーは、前記同種ポジティブコントロールドナーとして選択された。前記残りの6種類の血液ドナーはレシピエントとして選択された。前記同種ポジティブコントロールドナーと胎盤由来細胞系がマイトマイシンCで処理され、前記6種類の個別同種レシーバーを用いた混合リンパ球反応で培養された。1プレート当たり3種類のレシーバーを用いた2種類の細胞培養プレートを用い、反応は3回行われた(表11−2)。前記平均刺激指数は1.3(プレート2)から3(プレート1)の範囲で、前記同種ドナーのポジティブコントロールは46.25(プレート2)から279(プレート1)の範囲であった(表11−3)。
Bruder SP et.al.USP 6,355,239 B1(2002)
Abbas,AK,Lichtman,AH Cellular and Molecular Immunology 5th Ed.(2003)Saunders,Philadelphia,p.171
Bouteiller P.Le et.al.,(2003)Placenta 24;S10〜S15
Coumans B et.al.,(1999)Journal of Immunological Methods 224,185〜196]
Brown,Julia et.al.(2003)The Journal of Immunology 170,1257〜1266
胎盤および臍帯由来PPDCから選択された栄養因子の分泌が測定された。血管由来活性(つまり、肝細胞増殖因子(HGF)(Rosen et al.(1997)Ciba Found.Symp.212:215〜26)、単球走化性因子1(MCP−1)(Salcedo et al.(2000)Blood 96;34〜40)、インターロイキン−8(IL−8)( Li et al.(2003)J.Immunol.170:3369〜76)、角化細胞増殖因子(KGF)、塩基性線維芽細胞増殖因子(bFGF)、血管内皮細胞増殖因子(VEGF)(Hughes et al.(2004)Ann.Thorac.Surg.77:812〜8)、組織マトリックスメタロプロテアーゼ阻害物質1(TIMP1)、アンジオポエチン2(ANG2)、血小板由来増殖因子(PDGF−bb)、トロンボポエチン(TPO)、ヘパリン結合上皮細胞増殖因子(HB−EGF)、間質由来因子1a(SDF−1a))、神経栄養性/神経保護活性(脳由来神経栄養因子(BDNF)(Cheng et al.(2003)Dev.Biol.258;319〜33)、インターロイキン−6(IL−6)、顆粒球走化性タンパク質−2(GCP−2)、トランスフォーミング増殖因子β2(TGFβ2))、またはケモカイン活性(マクロファージ炎症性タンパク質1a(MIP1a)、マクロファージ炎症性タンパク質1β(MIP1b)、単球遊走因子−1(MCP−1)、Rantes(活性制御、正常T細胞の発現と分泌)、I309、thymus and activation−regulated chemokine(TARC)、Eotaxin、マクロファージ由来ケモカイン(MDC)、IL−8)を有する因子が選択された。
細胞培養:胎盤と臍帯由来のPPDC、およびヒト新生児包皮由来のヒト線維芽細胞は、ゼラチンコーティングしたT75フラスコで増殖培地(DMEM−低グルコース(Gibco、カリフォルニア州カールズバッド)、15%(v/v)ウシ胎仔血清(SH30070.03;Hyclone、ユタ州ローガン)、50ユニット/ミリリットルのペニシリン、50マイクログラム/ミリリットルのストレプトマイシン(Gibco))に培養された。細胞は継代11で凍結保存され、液体窒素に保存された。前記細胞を解凍後、増殖培地が前記細胞に追加された後、15ミリリットルの遠心分離チューブに移し、150xgで5分間、前記細胞を遠心分離した。前記上清は廃棄された。前記細胞ペレットは4ミリリットルの増殖培地に再懸濁され、細胞が計数された。細胞は増殖培地15ミリリットルを含むT75フラスコに5,000細胞/cm2で播種され、24時間培養された。前記培地は8時間、無血清培地(DMEM−低グルコース(Gibco)、0.1%(w/v)ウシ血清アルブミン(Sigma)、50ユニット/ミリリットルのストレプトマイシン、50マイクログラム/ミリリットルのストレプトマイシン(Gibco))に変更された。無血清条件培地はインキュベーションの最後に回収され、14,000xgで5分間遠心分離され、−0℃で保存された。各フラスコの細胞数を推定するため、細胞はリン酸緩衝生理食塩水(PBS)で洗浄され、2ミリリットルのトリプシン/EDTA(Gibco)を用いて分離された。トリプシン活性は8ミリリットルの増殖培地を加えることで抑制された。細胞は150xgで5分間遠心分離された。上清は除去され、細胞は1ミリリットルの増殖培地に再懸濁された。血球計数板を用い、細胞数が推定された。
ELISAアッセイ:MCP−1およびIL−6は、胎盤および臍帯由来PPDCと皮膚線維芽細胞により分泌された(表12−1)。臍帯由来細胞は、他の細胞集団よりも少なくとも10倍多い量のMCP−1とIL6を分泌した。GCP−2およびIL−8は、臍帯由来PPDCにより多く発現された。TGF−β2は検出されなかった。VEGFは線維芽細胞培地で検出された。
Le Belle JE,Svendsen CN.(2002)Stem cells for neurodegenerative disorders: where can we go from here? BioDrugs.16;389〜401.
Rosen EM,Lamszus K,Laterra J,Polverini PJ,Rubin JS,Goldberg ID.(1997)HGF/SF in angiogenesis. Ciba Found Symp.212;215〜26,.
Salcedo R,Ponce ML,Young HA,Wasserman K,Ward JM,Kleinman HK,Oppenheim JJ,Murphy WJ.(2000)Human endothelial cells express CCR2 and respond to MCP−1: direct role of MCP−1 in angiogenesis and tumor progression.Blood.96;34〜40.
Li A,Dubey S,Varney ML,Dave BJ,Singh RK(2003)IL−8 directly enhanced endothelial cell survival,proliferation,and matrix metalloproteinases production and regulated angiogenesis.J Immunol.170;3369〜76.
Hughes GC,Biswas SS,Yin B,Coleman RE,DeGrado TR,Landolfo CK,Lowe JE,Annex BH,Landolfo KP.(2004)Therapeutic angiogenesis in chronically ischemic porcine myocardium: comparative effects of bFGF and VEGF.Ann Thorac Surg.77;812〜8.
Cheng A,Wang S,Cai J,Rao MS,Mattson MP(2003)Nitric oxide acts in a positive feedback loop with BDNF to regulate neural progenitor cell proliferation and differentiation in the mammalian brain.Dev Biol.258;319〜33.
Sebire G,Emilie D,Wallon C,Hery C,Devergne O,Delfraissy JF,Galanaud P,Tardieu M.(1993)In vitro production of IL−6,IL−1 beta,and tumor necrosis factor−alpha by human embryonic microglial and neural cells.J Immunol.150;1517〜23.
細胞が前記作用部位を標的とすることができる特定の応用について、細胞療法は全身に注入されてもよい。注入された細胞が、致死的と考えられる血栓症を引き起こさないことが重要である。組織因子、つまり膜結合凝血促進性糖タンパク質は外因性凝固カスケードのイニシエーターであり、これはin vivoで主な凝固経路である。組織因子も、例えば、前記原始的血管壁の形成において、胚血管新生に重要な役割を果たす(Brodsky et al.(2002)Exp.Nephrol.10:299〜306)。最初の凝固に対してPPDCの能力を決定するため、臍帯と胎盤由来PPDCで組織因子の発現と血漿凝固を開始するその能力が評価された。
ヒト組織因子:ヒト組織因子のSIMPLASTIN(Organon Tekailca Corporation、ノースカロライナ州ダラム)は、20ミリリットルの蒸留水でもどされた。前記原液は8本のチューブで連続的に蒸留された(1:2)。正常なヒト血漿(George King Bio−Medical、カンザス州オーバーランドパーク)が水浴中37℃で解凍され、使用前に氷中に保存された。96ウェルプレートの各ウェルに、100マイクロリットルのリン酸緩衝生理食塩水(PBS)、10マイクロリットルの希釈Simplastin(登録商標)(ブランクのウェルを除く)、30マイクロリットルの0.1モル塩化カルシウム、100マイクロリットルの正常ヒト血漿が追加された。前記プレートは直ちに温度制御マイクロプレートリーダーに設置され、吸光度は405ナノメーター、40秒間隔で、30分測定した。
フローサイトメトリー分析では、胎盤および臍帯由来分娩後由来細胞のいずれも組織因子を表現していることが明らかとなった。血漿凝固アッセイは、組織因子が活性であることを証明した。胎盤および臍帯由来細胞のいずれにおいても、半減期吸光度までの時間(T1/2 to max、表13−1)で示されるとおり、凝固率が上昇した。凝固は初期(P5)および後期(P18)細胞の両方で観察された。前記T1/2 to maxはJ82細胞数と反比例している。組織因子に対する抗体であるCNTO 859を用いた臍帯細胞のプレインキュベーションは前記凝固反応を抑制し、それによって組織因子が前記凝固の原因となっていることを示した。
Doshi and Marmur,Critical Care Med.,30:S241〜S250(2002)
Moll and Ortel,Ann.Intern.Med.,127:177〜185(1997)
血管新生、または新しい脈管構造の形成は、新しい組織の増殖に必要である。血管新生の誘導は、多くの病的状態に重要な治療目的である。本研究は、in vitroアッセイで前記分娩後由来細胞に考えられる血管由来活性を同定することを目的としていた。前記研究の後、基底膜抽出液であるMATRIGEL(BD Discovery Labware、マサチューセッツ州ベッドフォード)でコーティングした培養皿に内皮細胞を播種する、十分に確立された方法を行った(Nicosia and Ottinetti(1990)In Vitro Cell Dev.Biol.26(2):119〜28)。MATRIGEL(BD Discovery Labware、マサチューセッツ州ベッドフォード)で内皮細胞に血管新生因子を処理すると前記細胞を刺激し、毛細管現象と同様のネットワークを形成する。血管新生の刺激物質と阻害物質を治療するため、これは一般的なin vitroアッセイである(Ito et al.(1996)Int.J.Cancer 67(1):148〜52)。本研究では共培養系を利用し、前記分娩後由来細胞を培養ウェルインサートに播種した。これらの透過性インサートでは、前記内皮および前記分娩後由来細胞の培地成分を受動的に交換することが可能である。
細胞培地:分娩後組織由来細胞。ヒト臍帯および胎盤が受理され、細胞はこれまでの説明どおり単離された(例1)。ゼラチンコーティングした組織培養プラスチックフラスコで、増殖培地(ダルベッコ変法基本培地(DMEM;Invitrogen、カリフォルニア州カールズバッド)、15%(v/v)ウシ胎仔血清(Hyclone、ユタ州ローガン)、100ユニット/ミリリットルのペニシリン、100マイクログラム/ミリリットルのストレプトマイシン(Invitrogen)、0.001%(v/v)2−メルカプトエタノール(Sigma、ミズーリー州セントルイス))中、細胞が培養された。前記培地は37℃で5%CO2によりインキュベートされた。実験に使用された細胞は、継代4〜12であった。
胎盤由来細胞または臍帯由来細胞を用いた共培養系で、HUVECが細胞ネットワークを形成する(データは示されていない)。HUVEC細胞は、hMSCおよび10ナノモルのbFGFを用い、共培養実験で限定された細胞ネットワークを形成する(データは示されていない)。治療を行わないHUVEC細胞で示されたネットワークの形成は、非常に少ないか、全くなかった(データは示されていない)。これらの結果は、前記分娩後由来細胞が前記HUVECを刺激する血管新生因子を放出することを示唆している。
前記分娩後臍帯と胎盤由来の細胞は、再生治療に有用である。生物分解性物質を用い、SCIDマウスに移植した分娩後由来細胞で作られた組織が評価された。評価された物質は、VICRYL不織布、35/65 PCL/PGA発砲体、RAD 16自己集合性ペプチドヒドロゲルであった。
細胞培地:胎盤由来細胞と臍帯由来細胞は、ゼラチンコーティングしたフラスコ中、増殖培地(DMEM−低グルコース(Gibco、カリフォルニア州カールズバッド)、15%(v/v)ウシ胎仔血清(Cat.#SH30070.03;Hyclone、ユタ州ローガン)、0.001%(v/v)βメルカプトエタノール(Sigma、ミズーリー州セントルイス)、50ユニット/ミリリットルのペニシリン、50マイクログラム/ミリリットルのストレプトマイシン(Gibco))で増殖された。
1.VICRYL不織布+1×106臍帯由来細胞
2.35/65 PCL/PGA発砲体+1×106臍帯由来細胞
3.RAD 16自己集合性ペプチド+1×106臍帯由来細胞
4.VICRYL不織布+1×106臍帯由来細胞
5.35/65 PCL/PGA発砲体+1×106胎盤由来細胞
6.RAD 16自己集合性ペプチド+1×106胎盤由来細胞
7.35/65 PCL/PGA発砲体
8.VICRYL不織布
30日後、SCIDマウスに皮下移植された発砲体に組織が最小限内側に伸びていた(データは示されていない)。対照的に、発砲体で満たされた広範な組織に、臍帯由来細胞または胎盤由来細胞が移植されていた(データは示されていない)。
Claims (29)
- 軟組織疾患の治療、又は血管新生因子を必要とする患者の治療において使用される、実質的に均一な細胞集団を含む細胞組成物であって、
前記細胞集団は、実質的に血液を含まないヒト臍帯組織から単離される、単離臍帯組織細胞を有し、この集団は、培養において自己複製および増殖し、他の表現型に分化する潜在性を有し、少なくとも40継代可能であり、更に以下の、
(a)CD10、CD13、CD44、CD73、CD90、PDGFr−α、PDL2、HLA−A、B、Cのそれぞれを産生し、
(b)CD31、CD34、CD45、CD80、CD86、CD117、CD141、CD178、B7−H2、HLA−G、HLA−DR、DP、DQのいずれも発現せず、
(c)線維芽細胞、間葉幹細胞、または腸骨稜骨髄細胞であるヒト細胞と比較して、インターロイキン8、レチキュロン1、及びケモカイン(C−X−Cモチーフ)リガンド3の増加した発現
という特徴を有するものである、細胞組成物。 - 請求項1記載の細胞組成物において、前記単離臍帯組織細胞は、更に、1若しくはそれ以上の以下の特徴、
(a)MCP−1、MIP1ベータ、IL−6、IL−8、GCP−2、HGF、KGF、FGF、HB−EGF、BDNF、TPO、RANTES、及びTIMP1の因子をそれぞれ分泌し、
(b)SDF−1アルファ、TGF−ベータ2、ANG2、PDGFbb、MIP1a、及びVEGFのいずれの因子も分泌しない、
の特徴を有する、細胞組成物。 - 請求項1又は2記載の細胞組成物において、
前記細胞は、軟組織表現型に分化するように誘導されるものである、細胞組成物。 - 請求項3記載の細胞組成物において、
前記軟組織の表現型は、軟骨組織、半月組織、靱帯組織、腱組織、椎間板組織、歯周組織、皮膚組織、血管組織、筋肉組織、筋膜組織、骨膜組織、心膜組織、肺組織、滑膜組織、腎組織、骨髄、泌尿生殖器組織、腸組織、肝組織、膵臓組織、脾臓組織、または脂肪組織の細胞の表現型である、細胞組成物。 - 請求項1又は2記載の細胞組成物において、
前記軟組織は、軟骨組織、半月組織、靱帯組織、腱組織、椎間板組織、歯周組織、皮膚組織、血管組織、筋肉組織、筋膜組織、骨膜組織、心膜組織、肺組織、滑膜組織、腎組織、骨髄、泌尿生殖器組織、腸組織、肝組織、膵臓組織、脾臓組織、または脂肪組織である、細胞組成物。 - 請求項1又は2記載の細胞組成物であって、さらに、
骨髄細胞、脂肪細胞、幹細胞、角化細胞、血管内皮細胞、筋芽細胞、筋細胞、間質細胞、および他の軟組織前駆細胞の少なくとも1つの細胞型を有するものである、細胞組成物。 - 請求項1又は2記載の細胞組成物であって、さらに、1若しくはそれ以上の生理活性因子を有する、細胞組成物。
- 請求項7記載の細胞組成物において、
前記生理活性因子は、分化誘導因子、抗アポトーシス薬、抗炎症薬、免疫抑制薬/免疫調節薬、抗増殖薬、コルチコステロイド、抗体、抗血栓形成薬、抗酸化剤、および瘢痕抑制因子の少なくとも1つである、細胞組成物。 - 請求項1記載の細胞組成物において、前記細胞集団は、細胞外マトリックスを含むものである、細胞組成物。
- 請求項9記載の細胞組成物において、前記マトリックスは、3次元足場を有するものである、細胞組成物。
- 請求項10記載の細胞組成物において、前記足場は、平面、チューブ状、又は多層である、細胞組成物。
- 請求項1〜3及び9のいずれか1つに記載の細胞組成物を含む薬学的組成物。
- 請求項12記載の薬学的組成物において、
前記組成物は、軟組織疾患を治療するために有効な量の前記細胞を有するものである、薬学的組成物。 - 請求項13記載の薬学的組成物において、更に、幹細胞、上皮細胞、皮膚線維芽細胞、メラニン形成細胞、角化細胞、および他の上皮前駆細胞の少なくとも1つの他の細胞型を含むものである、薬学的組成物。
- 請求項1又は2記載の細胞組成物を培地中に含む、細胞培養物。
- 軟組織細胞を(i)請求項1又は2記載の細胞組成物に暴露することにより、軟組織細胞に対して、栄養学的サポートを提供するインビトロの方法。
- 請求項16記載のインビトロの方法において、
前記軟組織細胞は、幹細胞、筋細胞、筋芽細胞、角化細胞、メラニン形成細胞、皮膚線維芽細胞、骨髄細胞、脂肪細胞、上皮細胞、内皮細胞、または間質細胞である、方法。 - 請求項16記載のインビトロの方法において、
前記軟組織細胞は、大動脈内皮細胞、冠動脈内皮細胞、肺動脈内皮細胞、腸骨動脈内皮細胞、微小血管内皮細胞、臍動脈内皮細胞、臍静脈内皮細胞、および内皮前駆細胞の少なくとも1つを有するものである、方法。 - (i)請求項1又は2記載の細胞組成物に軟組織細胞の集団を曝露させる工程を有する、血管新生を誘導するインビトロの方法。
- 請求項19記載のインビトロの方法において、
前記軟組織細胞は、幹細胞、筋細胞、筋芽細胞、角化細胞、メラニン形成細胞、骨髄細胞、脂肪細胞、上皮細胞、内皮細胞、または間質細胞である、方法。 - 請求項19記載のインビトロの方法において、
前記軟組織細胞は、大動脈内皮細胞、冠動脈内皮細胞、肺動脈内皮細胞、腸骨動脈内皮細胞、微小血管内皮細胞、臍動脈内皮細胞、臍静脈内皮細胞、内皮前駆細胞の少なくとも1つを有するものである、方法。 - 軟組織疾患を治療するために使用される、請求項1、2、9のいずれかに記載の細胞組成物。
- 請求項22記載の細胞組成物において、前記軟組織疾患は、先天性欠陥、ヘルニア、前記骨盤底の損傷、腱または靱帯の裂傷または破裂、瘢痕、熱傷、潰瘍、外科創傷、外傷、血管疾患、または筋疾患である、細胞組成物。
- 請求項22記載の細胞組成物において、
前記治療は、軟部組織の修復、再構築、充填、美容整形術、治療、組織増加、および組織の密封の少なくとも1つを有するものである、細胞組成物。 - 請求項1記載の細胞組成物、およびマトリックス、水和剤、細胞培養マトリックス、生物活性因子、第2の細胞タイプ、分化誘導剤、および細胞培地の少なくとも1つの付加的構成成分を有するキット。
- 請求項25記載のキットにおいて、前記マトリックスは、3次元足場である、キット。
- 請求項26記載のキットにおいて、前記細胞は、前記足場に播種されるものである、キット。
- 血管ネットワークを産生するインビトロの方法であって、請求項1、2、9のいずれかに記載の細胞組成物に軟組織細胞の集団を曝露させる工程を有する、方法。
- 請求項28記載のインビトロの方法において、前記軟組織細胞は、大動脈内皮細胞、冠動脈内皮細胞、肺動脈内皮細胞、腸骨動脈内皮細胞、微小血管内皮細胞、臍動脈内皮細胞、臍静脈内皮細胞の少なくとも1つを有するものである、方法。
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Families Citing this family (536)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20080077251A1 (en) * | 1999-06-07 | 2008-03-27 | Chen Silvia S | Cleaning and devitalization of cartilage |
US8563232B2 (en) | 2000-09-12 | 2013-10-22 | Lifenet Health | Process for devitalizing soft-tissue engineered medical implants, and devitalized soft-tissue medical implants produced |
US20020095157A1 (en) * | 1999-07-23 | 2002-07-18 | Bowman Steven M. | Graft fixation device combination |
US6179840B1 (en) | 1999-07-23 | 2001-01-30 | Ethicon, Inc. | Graft fixation device and method |
US8147824B2 (en) | 1999-08-05 | 2012-04-03 | Athersys, Inc. | Immunomodulatory properties of multipotent adult progenitor cells and uses thereof |
US20030032179A1 (en) * | 2000-12-06 | 2003-02-13 | Hariri Robert J. | Post-partum mammalian placenta, its use and placental stem cells therefrom |
AU2002220209B2 (en) * | 2000-12-06 | 2006-05-25 | Robert J. Hariri | Method of collecting placental stem cells |
US7311905B2 (en) * | 2002-02-13 | 2007-12-25 | Anthrogenesis Corporation | Embryonic-like stem cells derived from post-partum mammalian placenta, and uses and methods of treatment using said cells |
US20080152629A1 (en) * | 2000-12-06 | 2008-06-26 | James Edinger | Placental stem cell populations |
CA2365376C (en) | 2000-12-21 | 2006-03-28 | Ethicon, Inc. | Use of reinforced foam implants with enhanced integrity for soft tissue repair and regeneration |
KR101012952B1 (ko) * | 2001-02-14 | 2011-02-08 | 안트로제네시스 코포레이션 | 산후 포유류의 태반, 이의 용도 및 태반 줄기세포 |
WO2003008535A2 (en) * | 2001-07-20 | 2003-01-30 | Technion Research And Development Foundation Ltd. | Methods of generating human cardiac cells and tissues and uses thereof |
US7677565B2 (en) | 2001-09-28 | 2010-03-16 | Shuffle Master, Inc | Card shuffler with card rank and value reading capability |
US7736892B2 (en) * | 2002-02-25 | 2010-06-15 | Kansas State University Research Foundation | Cultures, products and methods using umbilical cord matrix cells |
US20080299090A1 (en) * | 2002-02-25 | 2008-12-04 | Kansas State University Research Foundation | Use Of Umbilical Cord Matrix Cells |
US20080003258A1 (en) * | 2002-10-16 | 2008-01-03 | Marcum Frank D | Composition and Method for Treating Rheumatoid Arthritis |
US20040078090A1 (en) | 2002-10-18 | 2004-04-22 | Francois Binette | Biocompatible scaffolds with tissue fragments |
US7824701B2 (en) | 2002-10-18 | 2010-11-02 | Ethicon, Inc. | Biocompatible scaffold for ligament or tendon repair |
KR101042448B1 (ko) * | 2002-11-26 | 2011-06-16 | 안트로제네시스 코포레이션 | 세포요법제, 세포요법제 단위 및 이를 이용한 치료방법 |
WO2004069172A2 (en) | 2003-01-30 | 2004-08-19 | The Government of the United States of America as represented by the Department of Veterans Affairs | Multilineage-inducible cells and uses thereof |
JP4790592B2 (ja) | 2003-02-11 | 2011-10-12 | ダビース,ジヨン・イー | ヒト臍帯のウォートンジェリーからの前駆細胞 |
NZ566132A (en) * | 2003-02-13 | 2009-09-25 | Anthrogenesis Corp | Use of umbilical cord blood to treat inflammation, ParkinsonÆs disease or diabetes |
US8197837B2 (en) | 2003-03-07 | 2012-06-12 | Depuy Mitek, Inc. | Method of preparation of bioabsorbable porous reinforced tissue implants and implants thereof |
CN100377165C (zh) * | 2003-04-24 | 2008-03-26 | 皇家飞利浦电子股份有限公司 | 无创式左心室的容积测定 |
US9592258B2 (en) | 2003-06-27 | 2017-03-14 | DePuy Synthes Products, Inc. | Treatment of neurological injury by administration of human umbilical cord tissue-derived cells |
US8518390B2 (en) | 2003-06-27 | 2013-08-27 | Advanced Technologies And Regenerative Medicine, Llc | Treatment of stroke and other acute neural degenerative disorders via intranasal administration of umbilical cord-derived cells |
US8790637B2 (en) | 2003-06-27 | 2014-07-29 | DePuy Synthes Products, LLC | Repair and regeneration of ocular tissue using postpartum-derived cells |
EP1641913B1 (en) | 2003-06-27 | 2016-01-06 | DePuy Synthes Products, Inc. | Postpartum cells derived from umbilical cord tissue, and methods of making and using the same |
US8491883B2 (en) * | 2003-06-27 | 2013-07-23 | Advanced Technologies And Regenerative Medicine, Llc | Treatment of amyotrophic lateral sclerosis using umbilical derived cells |
US9572840B2 (en) | 2003-06-27 | 2017-02-21 | DePuy Synthes Products, Inc. | Regeneration and repair of neural tissue using postpartum-derived cells |
US7875272B2 (en) * | 2003-06-27 | 2011-01-25 | Ethicon, Incorporated | Treatment of stroke and other acute neuraldegenerative disorders using postpartum derived cells |
US8226715B2 (en) | 2003-06-30 | 2012-07-24 | Depuy Mitek, Inc. | Scaffold for connective tissue repair |
US10583220B2 (en) | 2003-08-11 | 2020-03-10 | DePuy Synthes Products, Inc. | Method and apparatus for resurfacing an articular surface |
ATE449608T1 (de) * | 2003-08-12 | 2009-12-15 | Tigenix Nv | Verwendung von cxcl6 chemokin bei der prävention oder reparatur von knorpeldefekten |
US8043614B2 (en) | 2004-03-09 | 2011-10-25 | Ahlfors Jan-Eric W | Autogenic living scaffolds and living tissue matrices: methods and uses thereof |
GB0321337D0 (en) * | 2003-09-11 | 2003-10-15 | Massone Mobile Advertising Sys | Method and system for distributing advertisements |
US7682828B2 (en) | 2003-11-26 | 2010-03-23 | Whitehead Institute For Biomedical Research | Methods for reprogramming somatic cells |
US7316822B2 (en) * | 2003-11-26 | 2008-01-08 | Ethicon, Inc. | Conformable tissue repair implant capable of injection delivery |
WO2005055929A2 (en) * | 2003-12-02 | 2005-06-23 | Celgene Corporation | Methods and compositions for the treatment and management of hemoglobinopathy and anemia |
US7901461B2 (en) * | 2003-12-05 | 2011-03-08 | Ethicon, Inc. | Viable tissue repair implants and methods of use |
JP2005168360A (ja) * | 2003-12-09 | 2005-06-30 | Olympus Corp | 生体組織補填体の検査方法、装置、細胞培養容器および培養状態検査方法 |
US20050176139A1 (en) * | 2004-01-12 | 2005-08-11 | Yao-Chang Chen | Placental stem cell and methods thereof |
WO2005071066A1 (en) * | 2004-01-23 | 2005-08-04 | Board Of Regents, The University Of Texas System | Methods and compositions for preparing pancreatic insulin secreting cells |
US11395865B2 (en) | 2004-02-09 | 2022-07-26 | DePuy Synthes Products, Inc. | Scaffolds with viable tissue |
JP2007530543A (ja) | 2004-03-22 | 2007-11-01 | オシリス セラピューティクス,インコーポレイテッド | 間葉幹細胞及びその使用法 |
US8137686B2 (en) | 2004-04-20 | 2012-03-20 | Depuy Mitek, Inc. | Nonwoven tissue scaffold |
US8221780B2 (en) * | 2004-04-20 | 2012-07-17 | Depuy Mitek, Inc. | Nonwoven tissue scaffold |
US7622108B2 (en) * | 2004-04-23 | 2009-11-24 | Bioe, Inc. | Multi-lineage progenitor cells |
CA2563518C (en) * | 2004-04-23 | 2014-09-02 | Bioe, Inc. | Multi-lineage progenitor cells |
US8765119B2 (en) * | 2004-05-06 | 2014-07-01 | University Of South Florida | Treating amyotrophic lateral sclerosis (ALS)with isolated aldehyde dehydrogenase-positive umbilical cord blood cells |
US20060083732A1 (en) * | 2004-06-30 | 2006-04-20 | Arlene Gwon | Hyaluronic acid in the enhancement of lens regeneration |
US8802651B2 (en) * | 2004-06-30 | 2014-08-12 | Abbott Medical Optics Inc. | Hyaluronic acid in the enhancement of lens regeneration |
KR101322889B1 (ko) | 2004-08-16 | 2013-10-30 | 셀리서치 코포레이션 피티이 리미티드 | 제대의 양막으로부터 줄기/전구세포의 추출 |
US20060045872A1 (en) | 2004-08-25 | 2006-03-02 | Universidad Autonoma De Madrid Ciudad Universitaria de Cantoblanco | Use of adipose tissue-derived stromal stem cells in treating fistula |
US20060069008A1 (en) * | 2004-09-28 | 2006-03-30 | Sanjay Mistry | Treatment of neurological deficits in the striatum or substanta nigra pars compacta |
US8039258B2 (en) * | 2004-09-28 | 2011-10-18 | Ethicon, Inc. | Tissue-engineering scaffolds containing self-assembled-peptide hydrogels |
US20080038316A1 (en) * | 2004-10-01 | 2008-02-14 | Wong Vernon G | Conveniently implantable sustained release drug compositions |
US7473678B2 (en) | 2004-10-14 | 2009-01-06 | Biomimetic Therapeutics, Inc. | Platelet-derived growth factor compositions and methods of use thereof |
US7842304B2 (en) * | 2004-10-29 | 2010-11-30 | Nexeon Medsystems, Inc. | Methods and apparatus for treating an injured nerve pathway |
US11660317B2 (en) | 2004-11-08 | 2023-05-30 | The Johns Hopkins University | Compositions comprising cardiosphere-derived cells for use in cell therapy |
US8017395B2 (en) | 2004-12-17 | 2011-09-13 | Lifescan, Inc. | Seeding cells on porous supports |
WO2006083394A2 (en) * | 2004-12-21 | 2006-08-10 | Ethicon, Inc. | Postpartum cells derived from placental tissue, and methods of making, culturing, and using the same |
US20060153815A1 (en) * | 2004-12-21 | 2006-07-13 | Agnieszka Seyda | Tissue engineering devices for the repair and regeneration of tissue |
WO2006101548A2 (en) * | 2004-12-21 | 2006-09-28 | Ethicon, Inc. | Postpartum cells derived from umbilical cord tissue, and methods of making, culturing, and using the same |
PL1831356T3 (pl) * | 2004-12-23 | 2017-07-31 | DePuy Synthes Products, Inc. | Komórki poporodowe pochodzące z tkanki pępowinowej i sposoby ich wytwarzania i stosowania |
EP1838842A2 (en) * | 2004-12-23 | 2007-10-03 | Ethicon, Incorporated | Treatment of osteochondral diseases using postpartum-derived cells and products thereof |
WO2006071777A2 (en) * | 2004-12-23 | 2006-07-06 | Ethicon Incorporated | Soft tissue repair and regeneration using postpartum-derived cells and cell products |
CA2592435C (en) | 2004-12-23 | 2017-03-28 | Ethicon, Incorporated | Treatment of stroke and other acute neural degenerative disorders using postpartum derived cells |
US20060182724A1 (en) * | 2005-02-15 | 2006-08-17 | Riordan Neil H | Method for expansion of stem cells |
JP4783909B2 (ja) | 2005-03-04 | 2011-09-28 | 国立大学法人京都大学 | 心臓組織由来の多能性幹細胞 |
US8153430B2 (en) * | 2005-03-31 | 2012-04-10 | Stemnion, Inc. | Methods related to surgery |
US20060222634A1 (en) | 2005-03-31 | 2006-10-05 | Clarke Diana L | Amnion-derived cell compositions, methods of making and uses thereof |
EP2460875A1 (en) * | 2005-03-31 | 2012-06-06 | Stemnion, Inc. | Amnion-derived cell compositions, methods of making and uses thereof |
US8999706B2 (en) * | 2005-04-12 | 2015-04-07 | The Trustees Of The University Of Pennsylvania | Methods for preparation of human hair-follicle derived multipotent adult stem cells |
US20100087546A1 (en) * | 2005-04-20 | 2010-04-08 | Biogenic Innovations, Llc | Use of dimethyl sulfone (msm) to reduce homocysteine levels |
WO2006113731A2 (en) * | 2005-04-20 | 2006-10-26 | University Of Florida Research Foundation, Inc. | Bone marrow-derived neurogenic cells and uses thereof |
CN101267831B (zh) * | 2005-04-25 | 2013-04-24 | 麻省理工学院 | 用于促进止血和其它生理活动的组合物和方法 |
AU2006202209B2 (en) * | 2005-05-27 | 2011-04-14 | Lifescan, Inc. | Amniotic fluid derived cells |
WO2006133052A2 (en) * | 2005-06-08 | 2006-12-14 | Centocor, Inc. | A cellular therapy for ocular degeneration |
GB0511723D0 (en) * | 2005-06-09 | 2005-07-13 | Smith & Nephew | Placental stem cells |
WO2006135899A2 (en) * | 2005-06-13 | 2006-12-21 | The Johns Hopkins University | Survival, differentiation and structural intergration of human neural stem cells grafted into the adult spinal cord |
US7838503B2 (en) * | 2005-06-15 | 2010-11-23 | Children's Medical Center Corporation | Methods for extending the replicative lifespan of cells |
US20150119794A1 (en) * | 2005-08-05 | 2015-04-30 | Gholam A. Peyman | Methods to regulate polarization and enhance function of cells |
US20140336514A1 (en) * | 2005-08-05 | 2014-11-13 | Gholam A. Peyman | Methods to regulate polarization and enhance function of cells |
US8480797B2 (en) | 2005-09-12 | 2013-07-09 | Abela Pharmaceuticals, Inc. | Activated carbon systems for facilitating use of dimethyl sulfoxide (DMSO) by removal of same, related compounds, or associated odors |
WO2007033082A2 (en) | 2005-09-12 | 2007-03-22 | Abela Pharmaceuticals, Inc. | Compositions comprising dimethyl sulfoxide (dmso) |
CA2622204C (en) | 2005-09-12 | 2016-10-11 | Abela Pharmaceuticals, Inc. | Systems for removing dimethyl sulfoxide (dmso) or related compounds, or odors associated with same |
WO2007033180A1 (en) | 2005-09-12 | 2007-03-22 | Abela Pharmaceuticals, Inc. | Materials for facilitating administration of dimethyl sulfoxide (dmso) and related compounds |
JP2007106760A (ja) * | 2005-09-16 | 2007-04-26 | Kenji Yoshida | 造血幹細胞増殖剤 |
EP2664337B1 (en) | 2005-09-27 | 2019-08-14 | TissueTech, Inc. | Amniotic membrane preparations and purified compositions and methods of use |
ES2452595T3 (es) | 2005-10-13 | 2014-04-02 | Anthrogenesis Corporation | Inmunomodulación usando células madre de la placenta |
ZA200803929B (en) * | 2005-10-13 | 2009-08-26 | Anthrogenesis Corp | Production of oligodendrocytes from placenta-derived stem cells |
JP4921767B2 (ja) * | 2005-10-14 | 2012-04-25 | 株式会社カネカ | 細胞の分化誘導方法 |
US10117900B2 (en) * | 2005-11-09 | 2018-11-06 | Athersys, Inc. | MAPC treatment of brain injuries and diseases |
US20070178067A1 (en) * | 2005-11-09 | 2007-08-02 | John Maier | System and method for cytological analysis by raman spectroscopic imaging |
US11000546B2 (en) | 2005-11-09 | 2021-05-11 | Athersys, Inc. | Immunomodulatory properties of MAPCs and uses thereof |
CA2629283A1 (en) * | 2005-11-14 | 2007-05-24 | The New England Medical Center Hospitals, Inc. | Methods for preparing cord matrix stem cells (cmsc) for long term storage and for preparing a segment of umbilical cord for cryopreservation |
KR20080084808A (ko) * | 2005-11-17 | 2008-09-19 | 바이오미메틱 세라퓨틱스, 인크. | rhPDGF-BB 및 생체적합성 매트릭스를 사용하는상악안면골 보강 |
PL1971681T3 (pl) | 2005-12-16 | 2018-01-31 | Depuy Synthes Products Inc | Kompozycje oraz sposoby do hamowania niepożądanej odpowiedzi immunologicznej w przypadku transplantacji z brakiem zgodności tkankowej |
WO2007073552A1 (en) * | 2005-12-19 | 2007-06-28 | Ethicon, Inc. | In vitro expansion of postpartum derived cells in roller bottles |
SG10201401805YA (en) | 2005-12-22 | 2014-08-28 | Jane Ennis | Viable cells from frozen umbilical cord tissue |
WO2007076522A2 (en) * | 2005-12-28 | 2007-07-05 | Ethicon, Incorporated | Treatment of peripheral vascular disease using postpartum-derived cells |
US9125906B2 (en) | 2005-12-28 | 2015-09-08 | DePuy Synthes Products, Inc. | Treatment of peripheral vascular disease using umbilical cord tissue-derived cells |
CN105106239A (zh) * | 2005-12-28 | 2015-12-02 | 伊西康公司 | 使用产后衍生细胞治疗外周血管疾病 |
KR20210122908A (ko) * | 2005-12-29 | 2021-10-12 | 안트로제네시스 코포레이션 | 태반 줄기 세포 집단 |
AU2006332679A1 (en) | 2005-12-29 | 2007-07-12 | Anthrogenesis Corporation | Co-culture of placental stem cells and stem cells from a second source |
AU2006332680A1 (en) * | 2005-12-29 | 2007-07-12 | Anthrogenesis Corporation | Improved composition for collecting and preserving placental stem cells and methods of using the composition |
US8241902B2 (en) | 2006-01-11 | 2012-08-14 | Technion Research & Development Foundation Ltd. | Preparation of adult stem cell-derived connective tissue progenitors |
US20080286249A1 (en) * | 2006-01-12 | 2008-11-20 | Varney Timothy R | Use of mesenchymal stem cells for treating genetic diseases and disorders |
US20070253931A1 (en) * | 2006-01-12 | 2007-11-01 | Osiris Therapeutics, Inc. | Use of mesenchymal stem cells for treating genetic diseases and disorders |
GB0600972D0 (en) * | 2006-01-18 | 2006-03-01 | Univ Leeds | Enrichment of cells |
US9944900B2 (en) * | 2006-01-18 | 2018-04-17 | Hemacell Perfusion | Pulsatile perfusion extraction method for non-embryonic pluripotent stem cells |
US8871198B2 (en) * | 2006-03-29 | 2014-10-28 | Stemnion, Inc. | Methods related to wound healing |
US7875451B2 (en) * | 2006-01-19 | 2011-01-25 | The University Of Washington | Formulation to improve survival of transplanted cells |
CA3124132A1 (en) | 2006-01-23 | 2007-08-02 | Abt Holding Company | Mapc therapeutics without adjunctive immunosuppressive treatment |
CA2640185A1 (en) * | 2006-01-24 | 2007-08-02 | Christopher J. Centeno | Mesenchymal stem cell isolation and transplantation method and system to be used in a clinical setting |
FR2896511B1 (fr) * | 2006-01-26 | 2012-10-26 | Centre Nat Rech Scient | Procede de culture de cellules issues du tissu adipeux et leurs applications. |
EP2311505B1 (en) * | 2006-02-09 | 2013-11-06 | BioMimetic Therapeutics, LLC | Compositions and methods for treating bone |
WO2007099534A2 (en) * | 2006-03-01 | 2007-09-07 | The Regenerative Medicine Institute | Compostions and populations of cells obtained from the umbilical cord and methods of producing the same |
EP1996698A1 (en) * | 2006-03-01 | 2008-12-03 | Cartela R&D AB | Expansion and differentiation of mesenchymal stem cells |
PT2548951E (pt) * | 2006-03-23 | 2016-06-14 | Pluristem Ltd | Métodos para expansão celular e usos de células e de meios condicionados produzidos através deles para terapia |
US20110171182A1 (en) * | 2006-03-23 | 2011-07-14 | Pluristem Ltd. | Methods for cell expansion and uses of cells and conditioned media produced thereby for therapy |
WO2007121443A2 (en) * | 2006-04-17 | 2007-10-25 | Bioe, Inc. | Differentiation of multi-lineage progenitor cells to respiratory epithelial cells |
US20090208466A1 (en) * | 2006-04-21 | 2009-08-20 | James Yoo | Ink-jet printing of tissues |
EP2010100B1 (en) | 2006-04-27 | 2018-11-28 | Johnson & Johnson Surgical Vision, Inc. | Materials comprising polysiloxane polymers for enhancement of lens regeneration |
US9456979B2 (en) * | 2006-04-27 | 2016-10-04 | Sri International | Adminstration of intact mammalian cells to the brain by the intranasal route |
US8741643B2 (en) | 2006-04-28 | 2014-06-03 | Lifescan, Inc. | Differentiation of pluripotent stem cells to definitive endoderm lineage |
PL2029149T3 (pl) | 2006-05-05 | 2017-12-29 | John E. Davies | Uprzywilejowane immunologicznie i modulacyjne komórki progenitorowe |
CN101483998A (zh) | 2006-05-11 | 2009-07-15 | 武部直子 | 收集和使用胎盘脐血干细胞的方法 |
US20080050814A1 (en) * | 2006-06-05 | 2008-02-28 | Cryo-Cell International, Inc. | Procurement, isolation and cryopreservation of fetal placental cells |
WO2007146105A2 (en) * | 2006-06-05 | 2007-12-21 | Cryo-Cell International, Inc. | Procurement, isolation and cryopreservation of fetal placental cells |
CN101501185A (zh) * | 2006-06-09 | 2009-08-05 | 人类起源公司 | 胎盘巢(placental niche)及其培养干细胞的用途 |
US8475788B2 (en) * | 2006-06-14 | 2013-07-02 | Stemnion, Inc. | Methods of treating spinal cord injury and minimizing scarring |
WO2007145889A1 (en) * | 2006-06-14 | 2007-12-21 | Stemnion, Inc. | Methods of treating spinal cord injury and minimizing scarring |
US20070292401A1 (en) * | 2006-06-20 | 2007-12-20 | Harmon Alexander M | Soft tissue repair and regeneration using stem cell products |
RU2009102643A (ru) * | 2006-06-28 | 2010-08-10 | Дзе Юниверсити Оф Канзас (Us) | Дифференцировка стволовых клеток из матрикса пуповины в клетки линии гепатоцитов |
US9161967B2 (en) | 2006-06-30 | 2015-10-20 | Biomimetic Therapeutics, Llc | Compositions and methods for treating the vertebral column |
AU2007269712B2 (en) | 2006-06-30 | 2013-02-07 | Biomimetic Therapeutics, Llc | PDGF-biomatrix compositions and methods for treating rotator cuff injuries |
US20080124276A1 (en) * | 2006-07-24 | 2008-05-29 | Lifeline Cell Technology | Synthetic cornea from retinal stem cells |
US7993918B2 (en) * | 2006-08-04 | 2011-08-09 | Anthrogenesis Corporation | Tumor suppression using placental stem cells |
US20080171158A1 (en) * | 2006-08-11 | 2008-07-17 | Aqua Resources Corporation | Nanoplatelet copper hydroxides and methods of preparing same |
US8822030B2 (en) | 2006-08-11 | 2014-09-02 | Aqua Resources Corporation | Nanoplatelet metal hydroxides and methods of preparing same |
US7671014B2 (en) * | 2006-08-14 | 2010-03-02 | Warsaw Orthopedic, Inc. | Flowable carrier matrix and methods for delivering to a patient |
US8372437B2 (en) | 2006-08-17 | 2013-02-12 | Mimedx Group, Inc. | Placental tissue grafts |
JP5656183B2 (ja) * | 2006-08-22 | 2015-01-21 | 国立大学法人 東京医科歯科大学 | 滑膜由来間葉幹細胞(MSCs)の軟骨・半月板再生への応用 |
US20080082170A1 (en) * | 2006-09-29 | 2008-04-03 | Peterman Marc M | Apparatus and methods for surgical repair |
US20080078411A1 (en) * | 2006-10-03 | 2008-04-03 | Restore Medical, Inc. | Tongue implant for sleep apnea |
US20080078412A1 (en) * | 2006-10-03 | 2008-04-03 | Restore Medical, Inc. | Tongue implant |
WO2008045498A1 (en) | 2006-10-12 | 2008-04-17 | Ethicon, Inc. | Kidney-derived cells and methods of use in tissue repair and regeneration |
EP1913869A3 (en) * | 2006-10-19 | 2008-12-10 | Esaote S.p.A. | Diagnostic imaging method and apparatus for the anatomical region of the pelvic floor |
DK2084268T3 (en) * | 2006-10-23 | 2019-01-21 | Celularity Inc | METHODS AND COMPOSITIONS FOR TREATING BONE JOIN DEFECTS WITH PLACENTACLE POPULATIONS |
EP2462895B1 (en) * | 2006-11-03 | 2016-11-02 | BioMimetic Therapeutics, LLC | Compositions and methods for arthrodetic procedures |
ES2524443T3 (es) * | 2006-11-13 | 2014-12-09 | DePuy Synthes Products, LLC | Expansión in vitro de células postparto usando microportadores |
US20080132803A1 (en) * | 2006-11-30 | 2008-06-05 | Hyman Friedlander | Method and system for doing business by mining the placental-chord complex |
AU2007332799A1 (en) * | 2006-12-07 | 2008-06-19 | Teva Pharmaceutical Industries Ltd. | Method of generation and expansion of tissue-progenitor cells and mature tissue cells from intact bone marrow or intact umbilical cord tissue |
WO2008082525A1 (en) * | 2006-12-19 | 2008-07-10 | National Stem Cell Inc | Umbilical cord stem cell secreted product derived topical compositions and methods of use thereof |
US20100303770A1 (en) * | 2006-12-28 | 2010-12-02 | John Maslowski | Methods for culturing dermal cells for treatment of skin injuries such as burns |
US7980000B2 (en) * | 2006-12-29 | 2011-07-19 | Applied Materials, Inc. | Vapor dryer having hydrophilic end effector |
US8506949B2 (en) | 2007-01-17 | 2013-08-13 | Stemnion, Inc. | Methods for modulating inflammatory and/or immune responses |
US8221741B2 (en) | 2007-01-17 | 2012-07-17 | Marshall Vivienne S | Methods for modulating inflammatory and/or immune responses |
EP2129775A1 (en) | 2007-02-12 | 2009-12-09 | Anthrogenesis Corporation | Hepatocytes and chondrocytes from adherent placental stem cells; and cd34+, cd45- placental stem cell-enriched cell populations |
DK2120977T3 (da) | 2007-02-12 | 2013-08-12 | Anthrogenesis Corp | Behandling af inflammatoriske sygdomme under anvendelse af placenta-stamceller |
US20100151025A1 (en) * | 2007-02-20 | 2010-06-17 | Biomimetic Therapeutics, Inc. | Prevention and treatment for osteonecrosis and osteoradionecrosis of the jaw |
AR065584A1 (es) * | 2007-03-01 | 2009-06-17 | Cryo Cell Internat Inc | Obtencion aislamiento y crioconservacion de celulas endometriales / menstruales |
WO2008109816A1 (en) * | 2007-03-08 | 2008-09-12 | Hemacell Perfusion, Inc. | Method for isolation of afterbirth derived cells |
US20100172830A1 (en) * | 2007-03-29 | 2010-07-08 | Cellx Inc. | Extraembryonic Tissue cells and method of use thereof |
CA3071055A1 (en) | 2007-04-07 | 2008-10-16 | Whitehead Institute For Biomedical Research | Reprogramming of somatic cells |
EP2139497B1 (en) * | 2007-04-13 | 2013-11-06 | Stemnion, INC. | Methods for treating nervous system injury and disease |
ATE530638T1 (de) | 2007-04-26 | 2011-11-15 | Univ Ramot | Pluripotente autologe stammzellen aus der mündlichen oder gastrointestinalen schleimhaut |
US8574567B2 (en) | 2007-05-03 | 2013-11-05 | The Brigham And Women's Hospital, Inc. | Multipotent stem cells and uses thereof |
EP2607477B1 (en) | 2007-05-03 | 2020-09-23 | The Brigham and Women's Hospital, Inc. | Multipotent stem cells and uses thereof |
US8114668B2 (en) * | 2007-05-14 | 2012-02-14 | Cardiac Pacemakers, Inc. | Composition for cold storage of stem cells |
US20100111914A1 (en) * | 2007-05-21 | 2010-05-06 | Yuanyuan Zhang | Stem cells from urine and methods for using the same |
KR20150041157A (ko) | 2007-05-21 | 2015-04-15 | 웨이크 포리스트 유니버시티 헬스 사이언시즈 | 소변으로부터의 전구 세포 및 이를 사용하는 방법 |
TWM322542U (en) * | 2007-05-23 | 2007-11-21 | Universal Scient Ind Co Ltd | Testing machine |
WO2008148105A1 (en) * | 2007-05-25 | 2008-12-04 | Medistem Laboratories, Inc. | Endometrial stem cells and methods of making and using same |
DE602007010434D1 (de) * | 2007-06-01 | 2010-12-23 | Allergan Inc | Gerät zur Erzeugung des zugspannungsinduzierten Wachstums von biologischem Gewebe |
US9693486B1 (en) * | 2007-06-14 | 2017-06-27 | Switch, Ltd. | Air handling unit with a canopy thereover for use with a data center and method of using the same |
US8273526B2 (en) | 2007-06-18 | 2012-09-25 | Children's Hospital & Research Center At Oakland | Method of isolating stem and progenitor cells from placenta |
US20090004253A1 (en) * | 2007-06-29 | 2009-01-01 | Brown Laura J | Composite device for the repair or regeneration of tissue |
US20090004271A1 (en) * | 2007-06-29 | 2009-01-01 | Brown Laura J | Morselized foam for wound treatment |
US9080145B2 (en) | 2007-07-01 | 2015-07-14 | Lifescan Corporation | Single pluripotent stem cell culture |
US9095562B2 (en) * | 2007-07-05 | 2015-08-04 | Regenerative Sciences, Inc. | Methods and compositions for optimized expansion and implantation of mesenchymal stem cells |
DE102007034679A1 (de) * | 2007-07-25 | 2009-01-29 | Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. | Materialzusammensetzungen, welche aus exokrinem Drüsengewebe erhaltene adulte Stammzellen enthalten, insbesondere zur Verwendung in der Regenerationsmedizin, z.B. zur Wiederherstellung von verletztem oder geschädigtem Myokardgewebe |
US20090024224A1 (en) | 2007-07-16 | 2009-01-22 | Chen Silvia S | Implantation of cartilage |
CN101835479A (zh) * | 2007-07-25 | 2010-09-15 | 佰欧益有限公司 | 多系祖细胞分化为软骨细胞 |
AU2008282922B2 (en) | 2007-07-27 | 2014-01-16 | Humacyte, Inc. | Compositions comprising human collagen and human elastin and methods for soft tissue augmentation |
DK2185693T3 (da) | 2007-07-31 | 2019-09-23 | Lifescan Inc | Differentiering af humane embryoniske stamceller |
WO2009020651A2 (en) * | 2007-08-08 | 2009-02-12 | Pervasis Therapeutics, Inc. | Materials and methods for treating skeletal system damage and promoting skeletal system repair and regeneration |
US20090062907A1 (en) * | 2007-08-31 | 2009-03-05 | Quijano Rodolfo C | Self-expanding valve for the venous system |
US20090068153A1 (en) * | 2007-09-06 | 2009-03-12 | Vitelli Francesca P | Cell composition for tissue regeneration |
CA2736663C (en) | 2007-09-07 | 2018-01-02 | Surgical Biologics, Llc. | Placental tissue grafts and improved methods of preparing and using the same |
EP2591789B2 (en) * | 2007-09-19 | 2022-07-20 | Pluristem Ltd. | Adherent cells from adipose or placenta tissues and use thereof in therapy |
WO2009042768A1 (en) * | 2007-09-25 | 2009-04-02 | University Of Pittsburgh-Of The Commonwealth System Of Higher Education | Triggerably dissolvable hollow fibers for controlled delivery |
KR101644659B1 (ko) * | 2007-09-26 | 2016-08-01 | 안트로제네시스 코포레이션 | 인간 태반 관류액으로부터의 혈관형성 세포 |
KR20210022148A (ko) * | 2007-09-28 | 2021-03-02 | 안트로제네시스 코포레이션 | 인간 태반 관류액 및 인간 태반-유래 중간체 천연 킬러 세포를 사용한 종양 억제 방법 |
US8034329B2 (en) * | 2007-10-05 | 2011-10-11 | Advanced Technologies And Regenerative Medicine, Llc | Repair and regeneration of renal tissue using human umbilical cord tissue-derived cells |
WO2009052209A2 (en) * | 2007-10-16 | 2009-04-23 | University Of Kansas | Isolation of stem cells and effective control of contamination |
US20120219737A1 (en) | 2007-10-19 | 2012-08-30 | University Of Medicine And Dentistry Of New Jersey | Production of extracellular matrix, conditioned media and uses thereof |
WO2009052459A1 (en) * | 2007-10-19 | 2009-04-23 | University Of Medicine And Dentistry Of New Jersey | A method of using an extracellular matrix to enhance cell transplant survival and differentiation |
KR20160040739A (ko) * | 2007-11-07 | 2016-04-14 | 안트로제네시스 코포레이션 | 조산 합병증의 치료에 있어서의 제대혈의 용도 |
US20110086080A1 (en) * | 2007-11-14 | 2011-04-14 | Osteosphere, Llc | Ex-vivo production of human demineralized bone matrix |
CN107574142B (zh) | 2007-11-27 | 2021-07-06 | 生命扫描有限公司 | 人胚胎干细胞的分化 |
WO2009085969A2 (en) * | 2007-12-19 | 2009-07-09 | Regenerative Sciences, Llc | Compositions and methods to promote implantation and engrafment of stem cells |
US20090163990A1 (en) * | 2007-12-19 | 2009-06-25 | Chunlin Yang | Decellularized omentum matrix and uses thereof |
US8236538B2 (en) | 2007-12-20 | 2012-08-07 | Advanced Technologies And Regenerative Medicine, Llc | Methods for sterilizing materials containing biologically active agents |
WO2009085216A2 (en) | 2007-12-20 | 2009-07-09 | Squicor | Compositions and methods for detecting or elimninating senescent cells to diagnose or treat disease |
ES2621610T3 (es) * | 2007-12-27 | 2017-07-04 | DePuy Synthes Products, Inc. | Tratamiento de la degeneración de discos intervertebrales utilizando células derivadas de tejido cordón umbilical humano |
US20100279413A1 (en) * | 2008-01-14 | 2010-11-04 | Zymes, Llc | Applications of ubiquinones and ubiquinols |
US8088163B1 (en) | 2008-02-06 | 2012-01-03 | Kleiner Jeffrey B | Tools and methods for spinal fusion |
CN102014977B (zh) | 2008-02-07 | 2015-09-02 | 生物模拟治疗有限责任公司 | 用于牵引成骨术的组合物和方法 |
WO2009098698A2 (en) * | 2008-02-07 | 2009-08-13 | Shahar Cohen | Compartmental extract compositions for tissue engineering |
US20090209456A1 (en) * | 2008-02-19 | 2009-08-20 | Iliana Sweis | Compositions and methods for improving facial and body aesthetics |
CA2715878C (en) | 2008-02-21 | 2017-06-13 | Centocor Ortho Biotech Inc. | Methods, surface modified plates and compositions for cell attachment, cultivation and detachment |
US8318485B2 (en) * | 2008-02-25 | 2012-11-27 | Natalie Gavrilova | Stem cell therapy for the treatment of diabetic retinopathy and diabetic optic neuropathy |
US20090220995A1 (en) * | 2008-02-28 | 2009-09-03 | Sachs David H | Multiple administrations of umbilicus derived cells |
CN102026546A (zh) | 2008-03-14 | 2011-04-20 | 再生科学有限责任公司 | 软骨修复的合成物和方法 |
US20090232782A1 (en) * | 2008-03-14 | 2009-09-17 | Yu-Show Fu | Method for treating brain ischemic injury through transplantation of human umbilical mesenchymal stem cells |
JP5773366B2 (ja) | 2008-04-21 | 2015-09-02 | ティシュー リジェネレイション セラピューティックス、インコーポレイテッド | 生物学的又は化学的作用物質に対する予防又はそれらの治療のために遺伝子改変されたヒト臍帯血管周囲細胞 |
US8623648B2 (en) * | 2008-04-24 | 2014-01-07 | Janssen Biotech, Inc. | Treatment of pluripotent cells |
US9480549B2 (en) | 2008-04-25 | 2016-11-01 | Allosource | Multi-layer tissue patches |
US9358320B2 (en) | 2008-04-25 | 2016-06-07 | Allosource | Multi-layer tissue patches |
WO2009134991A2 (en) * | 2008-04-30 | 2009-11-05 | Ethicon, Inc. | Tissue engineered blood vessel |
US20110143429A1 (en) * | 2008-04-30 | 2011-06-16 | Iksoo Chun | Tissue engineered blood vessels |
EP2294187A2 (en) * | 2008-05-21 | 2011-03-16 | BioE LLC | Differentiation of multi-lineage progenitor cells to pancreatic cells |
WO2010011407A2 (en) * | 2008-05-23 | 2010-01-28 | President And Fellows Of Harvard College | Methods of generating patterned soft substrates and uses thereof |
WO2009155069A1 (en) * | 2008-05-28 | 2009-12-23 | Allan Mishra | Compositions and methods for treating psychiatric and neurodegenerative disorders |
US9682173B2 (en) * | 2008-06-11 | 2017-06-20 | The Children's Mercy Hospital | Solutions for tissue engineering and methods of use |
EP2300611B1 (en) | 2008-06-13 | 2017-08-09 | Whitehead Institute for Biomedical Research | Programming and reprogramming of cells |
MX2010014304A (es) * | 2008-06-26 | 2011-02-15 | Kci Licensing Inc | Estimulacion de la formacion de cartilago utilizando el tratamiento de presion reducida. |
WO2009157559A1 (ja) * | 2008-06-27 | 2009-12-30 | 独立行政法人産業技術総合研究所 | 膵臓疾患又は糖尿病のための膵臓細胞再生移植用キット |
WO2010002785A1 (en) * | 2008-06-30 | 2010-01-07 | Centocor Ortho Biotech Inc. | Differentiation of pluripotent stem cells |
KR20180018839A (ko) | 2008-06-30 | 2018-02-21 | 얀센 바이오테크 인코포레이티드 | 만능 줄기 세포의 분화 |
US20100028307A1 (en) * | 2008-07-31 | 2010-02-04 | O'neil John J | Pluripotent stem cell differentiation |
KR101903049B1 (ko) * | 2008-08-20 | 2018-11-07 | 안트로제네시스 코포레이션 | 단리된 태반 세포를 사용한 혈종 또는 혈관경련수축 치료 |
KR20110050521A (ko) | 2008-08-20 | 2011-05-13 | 안트로제네시스 코포레이션 | 개선된 세포 조성물 및 그의 제조 방법 |
KR20110050688A (ko) | 2008-08-22 | 2011-05-16 | 안트로제네시스 코포레이션 | 태반 세포 집단을 이용한 골 결함의 치료 방법 및 골 결함 치료 조성물 |
CN105708862B (zh) | 2008-09-02 | 2020-11-06 | 普拉里斯坦有限公司 | 来自胎盘组织的粘附细胞及其在治疗中的用途 |
MX2011002555A (es) | 2008-09-09 | 2011-08-03 | Biomimetic Therapeutics Inc | Composiciones de factor de crecimiento derivadas de plaquetas y metodo para el tratamiento de lesiones de tendon y ligamentos. |
US20100069827A1 (en) * | 2008-09-12 | 2010-03-18 | Barry Neil Silberg | Pre-Surgical Prophylactic Administration of Antibiotics and Therapeutic Agents |
US9446227B2 (en) | 2008-09-12 | 2016-09-20 | Sonescence, Inc. | Ultrasonic dispersion of compositions in tissue |
BRPI0920030B1 (pt) | 2008-10-06 | 2019-03-26 | 3-D Matrix, Ltd. | Agente de oclusão do tecido, agentes hemostáticos, preventivos e de oclusão ou escleroterapia relacionados, e infusão do tecido mucosal |
WO2010048418A1 (en) * | 2008-10-22 | 2010-04-29 | The Trustees Of Columbia University In The City Of New York | Cartilage regeneration without cell transplantation |
EP2344631B1 (en) | 2008-10-31 | 2019-10-16 | Synthes GmbH | Method and device for activating stem cells |
US9234178B2 (en) | 2008-10-31 | 2016-01-12 | Janssen Biotech, Inc. | Differentiation of human pluripotent stem cells |
JP2012507289A (ja) * | 2008-10-31 | 2012-03-29 | ヤンセン バイオテツク,インコーポレーテツド | ヒト胚性幹細胞の膵内分泌系への分化 |
BRPI0921494A2 (pt) | 2008-11-03 | 2018-10-30 | Prad Reasearch And Development Ltd | método de planejamento de uma operação de amostragem para uma formação subterrãnea, método de contolar uma operação de amostragem de formação subterrânea, método de controlar uma operação de perfuração para uma formação subterrãnea, e método de realizar uma amostragem durante a operação de perfuração. |
AU2009316541B2 (en) * | 2008-11-19 | 2015-08-06 | Celularity Inc. | Amnion derived adherent cells |
MX356756B (es) | 2008-11-20 | 2018-06-11 | Centocor Ortho Biotech Inc | Células madre pluripotentes en microportadores. |
EP2366022B1 (en) | 2008-11-20 | 2016-04-27 | Janssen Biotech, Inc. | Methods and compositions for cell attachment and cultivation on planar substrates |
AU2009316594B2 (en) * | 2008-11-20 | 2014-05-01 | Lifecell Corporation | Method for treatment and prevention of parastomal hernias |
ES2731340T3 (es) * | 2008-11-21 | 2019-11-15 | Celularity Inc | Tratamiento de enfermedades, trastornos o afecciones pulmonares utilizando células placentarias |
US8366748B2 (en) | 2008-12-05 | 2013-02-05 | Kleiner Jeffrey | Apparatus and method of spinal implant and fusion |
WO2010065854A1 (en) | 2008-12-05 | 2010-06-10 | Regenerative Sciences, Llc | Methods and compositions to facilitate repair of avascular tissue |
WO2010064702A1 (ja) * | 2008-12-05 | 2010-06-10 | 国立大学法人 東京大学 | 癌の予後を予測するためのバイオマーカー |
US20100168022A1 (en) * | 2008-12-11 | 2010-07-01 | Centeno Christopher J | Use of In-Vitro Culture to Design or Test Personalized Treatment Regimens |
EP2379087B1 (en) * | 2008-12-19 | 2014-08-20 | DePuy Synthes Products, LLC | Umbilical cord tissue derived cells for treating neuropathic pain and spasticity |
US20130302283A1 (en) | 2012-05-14 | 2013-11-14 | Advanced Technologies And Regenerative Medicine, Llc | hUTC MODULATION OF PRO-INFLAMMATORY MEDIATORS OF LUNG AND PULMONARY DISEASES AND DISORDERS |
US10557116B2 (en) | 2008-12-19 | 2020-02-11 | DePuy Synthes Products, Inc. | Treatment of lung and pulmonary diseases and disorders |
EP2379089B1 (en) * | 2008-12-19 | 2019-04-17 | DePuy Synthes Products, Inc. | Regeneration and repair of neural tissue following injury |
US10179900B2 (en) * | 2008-12-19 | 2019-01-15 | DePuy Synthes Products, Inc. | Conditioned media and methods of making a conditioned media |
US8771677B2 (en) | 2008-12-29 | 2014-07-08 | Vladimir B Serikov | Colony-forming unit cell of human chorion and method to obtain and use thereof |
BRPI0918196A2 (pt) * | 2008-12-30 | 2016-03-01 | Kci Licensing Inc | sistema para aplicar um tratamento a uma area lesionada em um primeiro osso de dois ossos que formam uma articulação, metodo para aplicação de um tratamento a uma area lesionada no primeiro osso de dois osso que formam uma articulação, metodo de realização de cirurgia no joelho, uso do sistema de entrega de pressão reduzida e bexiga para a aplicação de um tratamento de uma area lesionada no primeiro osso de dois ossos que formam uma articulação |
JP5701614B2 (ja) * | 2009-01-23 | 2015-04-15 | 国立大学法人 東京大学 | 培養細胞の評価方法 |
US9247943B1 (en) | 2009-02-06 | 2016-02-02 | Kleiner Intellectual Property, Llc | Devices and methods for preparing an intervertebral workspace |
US20120142603A1 (en) * | 2009-02-12 | 2012-06-07 | University Of Southern California | Bioadhesive patch for sutureless closure of soft tissue |
KR101422690B1 (ko) * | 2009-02-27 | 2014-07-23 | (주)차바이오앤디오스텍 | 배아줄기세포 유래 혈관형성전구세포의 배양 분비물을 포함하는 피부재생용 조성물 및 이의 용도 |
EP2411505A4 (en) * | 2009-03-26 | 2013-01-30 | Univ California | MESENCHYMAL STEM CELLS PRODUCING INHIBITORY RNA WHICH CAN BE USED TO ACT IN THE COURSE OF A DISEASE |
AU2010229651B2 (en) * | 2009-03-26 | 2014-05-08 | Advanced Technologies And Regenerative Medicine, Llc | Human umbilical cord tissue cells as therapy for Alzheimer' s disease |
WO2010118059A1 (en) * | 2009-04-06 | 2010-10-14 | Capricor, Inc. | Systems and methods for cardiac tissue repair |
JP5972163B2 (ja) * | 2009-05-13 | 2016-08-17 | メディポスト カンパニー リミテッド | 幹細胞の細胞活性と関連したtsp−1、tsp−2、il−17br及びhb−egf並びにそれらの用途 |
AU2010249805B2 (en) * | 2009-05-20 | 2015-06-11 | Humacyte, Inc. | Elastin for soft tissue augmentation |
EP2434896A4 (en) * | 2009-05-28 | 2014-01-22 | Univ Central Florida Res Found | IN VITRO PRODUCTION OF OLIGODENDROCYTES FROM HUMAN UMBILICAL CORD STRAIN CELLS |
US20150335400A1 (en) * | 2009-06-17 | 2015-11-26 | The Trustees Of Columbia University In The City Of New York | Tooth scaffolds |
JP5819825B2 (ja) | 2009-07-20 | 2015-11-24 | ヤンセン バイオテツク,インコーポレーテツド | ヒト胚性幹細胞の分化 |
JP6219568B2 (ja) | 2009-07-20 | 2017-10-25 | ヤンセン バイオテツク,インコーポレーテツド | ヒト胚性幹細胞の分化 |
US8785185B2 (en) * | 2009-07-20 | 2014-07-22 | Janssen Biotech, Inc. | Differentiation of human embryonic stem cells |
ES2360434B1 (es) | 2009-07-21 | 2012-04-12 | Universitat Internacional De Catalunya | Celulas madre pluripotenciales obtenidas a partir de la pulpa dental. |
AU2010276201B2 (en) * | 2009-07-21 | 2013-10-17 | Abt Holding Company | Use of stem cells to reduce leukocyte extravasation |
WO2011022071A2 (en) * | 2009-08-20 | 2011-02-24 | The Regents Of The University Of California | Cardiac compositions |
US20110054929A1 (en) * | 2009-09-01 | 2011-03-03 | Cell Solutions Colorado Llc | Stem Cell Marketplace |
US8207651B2 (en) | 2009-09-16 | 2012-06-26 | Tyco Healthcare Group Lp | Low energy or minimum disturbance method for measuring frequency response functions of ultrasonic surgical devices in determining optimum operating point |
US9173694B2 (en) | 2009-09-18 | 2015-11-03 | Spinal Surgical Strategies, Llc | Fusion cage with combined biological delivery system |
USD750249S1 (en) | 2014-10-20 | 2016-02-23 | Spinal Surgical Strategies, Llc | Expandable fusion cage |
USD723682S1 (en) | 2013-05-03 | 2015-03-03 | Spinal Surgical Strategies, Llc | Bone graft delivery tool |
US8906028B2 (en) | 2009-09-18 | 2014-12-09 | Spinal Surgical Strategies, Llc | Bone graft delivery device and method of using the same |
US8685031B2 (en) | 2009-09-18 | 2014-04-01 | Spinal Surgical Strategies, Llc | Bone graft delivery system |
US10245159B1 (en) | 2009-09-18 | 2019-04-02 | Spinal Surgical Strategies, Llc | Bone graft delivery system and method for using same |
US10973656B2 (en) | 2009-09-18 | 2021-04-13 | Spinal Surgical Strategies, Inc. | Bone graft delivery system and method for using same |
US9060877B2 (en) | 2009-09-18 | 2015-06-23 | Spinal Surgical Strategies, Llc | Fusion cage with combined biological delivery system |
US9186193B2 (en) | 2009-09-18 | 2015-11-17 | Spinal Surgical Strategies, Llc | Fusion cage with combined biological delivery system |
US20170238984A1 (en) | 2009-09-18 | 2017-08-24 | Spinal Surgical Strategies, Llc | Bone graft delivery device with positioning handle |
US9629729B2 (en) | 2009-09-18 | 2017-04-25 | Spinal Surgical Strategies, Llc | Biological delivery system with adaptable fusion cage interface |
WO2011038133A2 (en) * | 2009-09-23 | 2011-03-31 | Davinci Biosciences Llc | Umbilical cord lining stem cells and methods and material for isolating and culturing same |
CA2777663A1 (en) | 2009-10-16 | 2011-04-21 | University Of Medicine And Dentistry Of New Jersey | Method for treating chronic nerve tissue injury using a cell therapy strategy |
EP2494035B1 (en) * | 2009-10-29 | 2018-02-28 | Janssen Biotech, Inc. | Pluripotent stem cells |
WO2011053874A1 (en) | 2009-10-30 | 2011-05-05 | Tandem Abela Development Group Llc | Dimethyl sulfoxide (dmso) and methylsulfonylmethane (msm) formulations to treat osteoarthritis |
US9113950B2 (en) | 2009-11-04 | 2015-08-25 | Regenerative Sciences, Llc | Therapeutic delivery device |
WO2011060079A1 (en) * | 2009-11-10 | 2011-05-19 | The Trustees Of Columbia University In The City Of New York | Compositions and methods for wound treatment |
WO2011062584A1 (en) * | 2009-11-19 | 2011-05-26 | Regents Of The University Of Minnesota | Reducing inflammation using cell therapy |
MX343786B (es) * | 2009-12-23 | 2016-11-22 | Janssen Biotech Inc | Diferenciacion de celulas madre embrionarias humanas. |
RU2664864C1 (ru) | 2009-12-23 | 2018-08-23 | Янссен Байотек, Инк. | Способы увеличения экспрессии ngn3 и nkx6.1 в эндокринных клетках поджелудочной железы |
EP3284818B1 (en) * | 2010-01-26 | 2022-03-09 | Celularity Inc. | Treatment of bone-related cancers using placental stem cells |
NZ601400A (en) | 2010-01-26 | 2013-11-29 | Stem Cells Spin S A | Cell homogenate from stem cells derived from growing deer antlers, a method of obtaining it and its use |
AR080222A1 (es) | 2010-02-18 | 2012-03-21 | Osiris Therapeutics Inc | Productos terapeuticos que comprenden dispersiones placentarias vitalizadas |
CN102753105B (zh) * | 2010-02-19 | 2015-09-30 | 生命细胞公司 | 腹壁治疗装置 |
AU2011217784B2 (en) | 2010-02-22 | 2014-10-09 | Biomimetic Therapeutics, Llc. | Platelet-derived growth factor compositions and methods for the treatment of tendinopathies |
JP6013196B2 (ja) * | 2010-03-01 | 2016-10-25 | ヤンセン バイオテツク,インコーポレーテツド | 多能性幹細胞から誘導した細胞を精製するための方法 |
KR20230054905A (ko) | 2010-04-07 | 2023-04-25 | 셀룰래리티 인코포레이티드 | 태반 줄기 세포를 사용한 혈관신생 |
WO2011127113A1 (en) | 2010-04-08 | 2011-10-13 | Anthrogenesis Corporation | Treatment of sarcoidosis using placental stem cells |
US9845457B2 (en) | 2010-04-30 | 2017-12-19 | Cedars-Sinai Medical Center | Maintenance of genomic stability in cultured stem cells |
US8529883B2 (en) | 2010-05-07 | 2013-09-10 | Fibrocell Technologies, Inc. | Dosage unit formulations of autologous dermal fibroblasts |
RU2587634C2 (ru) | 2010-05-12 | 2016-06-20 | Янссен Байотек, Инк. | Дифференцирование эмбриональных стволовых клеток человека |
US10130736B1 (en) | 2010-05-14 | 2018-11-20 | Musculoskeletal Transplant Foundation | Tissue-derived tissuegenic implants, and methods of fabricating and using same |
US9352003B1 (en) | 2010-05-14 | 2016-05-31 | Musculoskeletal Transplant Foundation | Tissue-derived tissuegenic implants, and methods of fabricating and using same |
US8883210B1 (en) | 2010-05-14 | 2014-11-11 | Musculoskeletal Transplant Foundation | Tissue-derived tissuegenic implants, and methods of fabricating and using same |
WO2011153236A1 (en) * | 2010-06-03 | 2011-12-08 | The Board Of Trustees Of The Leland Stanford Junior University | Purified compositions of cardiovascular progenitor cells |
PL2588027T3 (pl) | 2010-07-02 | 2017-09-29 | The University Of North Carolina At Chapel Hill | Rusztowania biomacierzowe do rozpraszania na skalę przemysłową |
WO2012009377A2 (en) | 2010-07-12 | 2012-01-19 | University Of Southern California | Biocompatible substrate for facilitating interconnections between stem cells and target tissues and methods for implanting same |
ES2666746T3 (es) | 2010-07-13 | 2018-05-07 | Anthrogenesis Corporation | Métodos para generar linfocitos citolíticos naturales |
US8825388B2 (en) | 2010-07-13 | 2014-09-02 | Qualcomm Incorporated | Indoor likelihood heatmap |
US20130203146A1 (en) * | 2010-08-03 | 2013-08-08 | Jackie Y. Ying | Microfabricated scaffold structures |
JP2012031127A (ja) * | 2010-08-03 | 2012-02-16 | Nagoya Univ | 臍帯由来間葉系幹細胞を含む組成物 |
IL207586A0 (en) | 2010-08-12 | 2010-12-30 | Omrix Biopharmaceuticals Ltd | A fibrin based therapeutic preparation and use thereof |
WO2012021885A1 (en) * | 2010-08-13 | 2012-02-16 | The Trustees Of Columbia University In The City Of New York | Three-dimensional tissue engineering devices and uses thereof |
JP2013536860A (ja) * | 2010-08-31 | 2013-09-26 | クック・ジェネラル・バイオテクノロジー・エルエルシー | 動物の疾病の治療のための全身的、同種間幹細胞治療 |
ES2585028T3 (es) | 2010-08-31 | 2016-10-03 | Janssen Biotech, Inc. | Diferenciación de células madre pluripotentes |
ES2659393T3 (es) | 2010-08-31 | 2018-03-15 | Janssen Biotech, Inc. | Diferenciación de células madre embrionarias humanas |
KR101851956B1 (ko) | 2010-08-31 | 2018-04-25 | 얀센 바이오테크 인코포레이티드 | 인간 배아 줄기 세포의 분화 |
US9725689B2 (en) | 2010-10-08 | 2017-08-08 | Terumo Bct, Inc. | Configurable methods and systems of growing and harvesting cells in a hollow fiber bioreactor system |
US8546338B2 (en) | 2010-12-08 | 2013-10-01 | Johnson & Johnson Consumer Companies, Inc. | Self-assembling hydrogels based on dicephalic peptide amphiphiles |
US8574899B2 (en) | 2010-12-22 | 2013-11-05 | Vladimir B Serikov | Methods for augmentation collection of placental hematopoietic stem cells and uses thereof |
US8969315B2 (en) | 2010-12-31 | 2015-03-03 | Anthrogenesis Corporation | Enhancement of placental stem cell potency using modulatory RNA molecules |
JP5388233B2 (ja) * | 2011-01-19 | 2014-01-15 | 富士ソフト株式会社 | 再生軟骨の軟骨特性を評価する方法 |
US8945536B2 (en) * | 2011-01-26 | 2015-02-03 | The Chinese University Of Hong Kong | Stem cell sheet for tissue repair |
WO2012154301A1 (en) * | 2011-03-18 | 2012-11-15 | Tornier, Inc. | Allogeneic microvascular tissue for soft tissue treatments |
EP2689008B1 (en) | 2011-03-22 | 2017-09-27 | Pluristem Ltd. | Methods for treating radiation or chemical injury |
WO2012148397A1 (en) | 2011-04-28 | 2012-11-01 | Aquero Company, Llc | Lysine-based polymer coagulants for use in clarification of process waters |
US10478206B2 (en) | 2011-04-29 | 2019-11-19 | University Of Southern California | Instruments and methods for the implantation of cell-seeded substrates |
US8877489B2 (en) | 2011-12-05 | 2014-11-04 | California Institute Of Technology | Ultrathin parylene-C semipermeable membranes for biomedical applications |
US8834928B1 (en) | 2011-05-16 | 2014-09-16 | Musculoskeletal Transplant Foundation | Tissue-derived tissugenic implants, and methods of fabricating and using same |
EP3851131A1 (en) * | 2011-05-31 | 2021-07-21 | LifeCell Corporation | Adipose tissue matrices |
PL2714059T3 (pl) | 2011-06-01 | 2019-04-30 | Celularity Inc | Leczenie bólu z użyciem komórek macierzystych łożyska |
ES2822301T3 (es) | 2011-06-10 | 2021-04-30 | Tissuetech Inc | Métodos de procesamiento de tejidos de soporte fetal |
US20140189897A1 (en) | 2011-06-21 | 2014-07-03 | Mayo Foundation For Medical Education And Research | Transgenic animals capable of being induced to delete senescent cells |
JP6243839B2 (ja) | 2011-06-29 | 2017-12-06 | バイオリストーラティブ セラピーズ, インコーポレイテッド | 褐色脂肪細胞の組成物および方法 |
US20130005829A1 (en) | 2011-06-30 | 2013-01-03 | Advanced Technologies And Regenerative Medicine, Llc. | Segmented, epsilon-Caprolactone-Rich, Poly(epsilon-Caprolactone-co-p-Dioxanone) Copolymers for Medical Applications and Devices Therefrom |
WO2013010045A1 (en) | 2011-07-12 | 2013-01-17 | Biotime Inc. | Novel methods and formulations for orthopedic cell therapy |
JP5937210B2 (ja) | 2011-08-10 | 2016-06-22 | デピュイ・シンセス・プロダクツ・インコーポレイテッド | 臍帯組織由来細胞を用いた末梢血管疾患の治療 |
WO2013055476A1 (en) | 2011-09-09 | 2013-04-18 | Anthrogenesis Corporation | Treatment of amyotrophic lateral sclerosis using placental stem cells |
US9248013B2 (en) | 2011-12-05 | 2016-02-02 | California Institute Of Technology | 3-Dimensional parylene scaffold cage |
US20140335074A1 (en) | 2011-12-13 | 2014-11-13 | Buck Institute For Research On Aging | Methods for improving medical therapies |
US9162011B2 (en) | 2011-12-19 | 2015-10-20 | Allosource | Flowable matrix compositions and methods |
ES2729712T3 (es) | 2011-12-20 | 2019-11-05 | Lifecell Corp | Productos de tejido de lámina |
BR112014014975B1 (pt) | 2011-12-20 | 2019-06-25 | Lifecell Corporation | Produto de tecido, e método para produzir uma composição de tecido |
US20130157365A1 (en) * | 2011-12-20 | 2013-06-20 | Advanced Technologies And Regenerative Medicine, Llc | Induced pluripotent stem cells from human umbilical cord tissue-derived cells |
RU2705001C2 (ru) | 2011-12-22 | 2019-11-01 | Янссен Байотек, Инк. | Дифференцировка эмбриональных стволовых клеток человека в одногормональные инсулинположительные клетки |
SG11201403465PA (en) | 2011-12-23 | 2014-10-30 | Atrm Llc | Detection of human umbilical cord tissue-derived cells |
SI3321355T1 (sl) | 2011-12-30 | 2021-11-30 | Amit Patel | Postopki in sestavki za klinično izpeljavo alogenske celice in terapevtske uporabe |
ES2705823T3 (es) | 2012-01-24 | 2019-03-26 | Lifecell Corp | Matrices de tejidos alargadas |
ES2666576T3 (es) * | 2012-02-23 | 2018-05-07 | Anthrogenesis Corporation | Identificación de compuestos antitumorales usando placenta |
US8940294B2 (en) | 2012-03-02 | 2015-01-27 | Tissuetech, Inc. | Methods of isolating and culturing stem cells |
CA2866590A1 (en) | 2012-03-07 | 2013-09-12 | Janssen Biotech, Inc. | Defined media for expansion and maintenance of pluripotent stem cells |
WO2013158664A2 (en) | 2012-04-17 | 2013-10-24 | Kythera Biopharmaceuticals, Inc. | Use of engineered viruses to specifically kill senescent cells |
EP3566727B1 (en) | 2012-04-24 | 2021-12-08 | LifeCell Corporation | Functionalized tissue matrices |
JP2015521054A (ja) | 2012-06-05 | 2015-07-27 | カプリコール,インコーポレイテッド | 心臓組織から心臓幹細胞を作製するための最適化方法および心臓治療におけるそれらの使用 |
JP6469003B2 (ja) | 2012-06-08 | 2019-02-13 | ヤンセン バイオテツク,インコーポレーテツド | 膵内分泌細胞へのヒト胚性幹細胞の分化 |
EP3466964A1 (en) | 2012-07-06 | 2019-04-10 | 3-D Matrix Ltd. | Fill-finish process for peptide solutions |
JP6282270B2 (ja) * | 2012-07-09 | 2018-02-21 | エフ.ホフマン−ラ ロシュ アーゲーF. Hoffmann−La Roche Aktiengesellschaft | 組み換えにより生成されたパエニバシラス・ポリミキサに由来する中性プロテアーゼ |
US11090338B2 (en) | 2012-07-13 | 2021-08-17 | Lifecell Corporation | Methods for improved treatment of adipose tissue |
US8960674B2 (en) | 2012-07-27 | 2015-02-24 | Bally Gaming, Inc. | Batch card shuffling apparatuses including multi-card storage compartments, and related methods |
WO2014028493A2 (en) | 2012-08-13 | 2014-02-20 | Cedars-Sinai Medical Center | Exosomes and micro-ribonucleic acids for tissue regeneration |
US9901081B2 (en) | 2012-08-23 | 2018-02-27 | Buck Institute For Research On Aging | Transgenic mouse for determining the role of senescent cells in cancer |
US9901080B2 (en) | 2012-08-23 | 2018-02-27 | Buck Institute For Research On Aging | Transgenic mouse having a transgene that converts a prodrug into a cytotoxic compound in senescent cells |
US11819522B2 (en) | 2012-09-19 | 2023-11-21 | Microvascular Tissues, Inc. | Compositions and methods for treating and preventing tissue injury and disease |
BR112015006055A2 (pt) | 2012-09-19 | 2017-07-04 | Microvascular Tissues Inc | composições e métodos para o tratamento e prevenção de lesão tecidual e doença |
US9872937B2 (en) | 2012-09-19 | 2018-01-23 | Microvascular Tissues, Inc. | Compositions and methods for treating and preventing tissue injury and disease |
US10596202B2 (en) | 2012-09-19 | 2020-03-24 | Microvascular Tissues, Inc. | Compositions and methods for treating and preventing tissue injury and disease |
CA2885327A1 (en) | 2012-09-26 | 2014-04-03 | Lifecell Corporation | Processed adipose tissue |
KR101728808B1 (ko) * | 2012-09-28 | 2017-04-20 | 한국생명공학연구원 | 아세카이니드 또는 이의 유도체를 포함하는 근력약화 관련 질환의 예방 또는 치료용 약학적 조성물 |
ITTO20120859A1 (it) * | 2012-10-02 | 2014-04-03 | Univ Degli Studi Torino | Nuova applicazione terapeutica di un mezzo condizionato da cellule staminali mesenchimali placentari |
US20150284689A1 (en) * | 2012-10-26 | 2015-10-08 | The Regents Of The University Of California | Strategy for engineering various 3d tissues, organoids and vasculature |
US10279018B2 (en) | 2012-12-03 | 2019-05-07 | Unity Biotechnology, Inc. | Immunogenic compositions for inducing an immune response for elimination of senescent cells |
US20140170748A1 (en) | 2012-12-14 | 2014-06-19 | DePuy Synthes Products, LLC | Nutrient Enriched Media for hUTC Growth |
US10370644B2 (en) | 2012-12-31 | 2019-08-06 | Janssen Biotech, Inc. | Method for making human pluripotent suspension cultures and cells derived therefrom |
EP2938723B1 (en) | 2012-12-31 | 2023-02-01 | Janssen Biotech, Inc. | Differentiation of human embryonic stem cells into pancreatic endocrine cells using hb9 regulators |
JP6557146B2 (ja) | 2012-12-31 | 2019-08-07 | ヤンセン バイオテツク,インコーポレーテツド | 多能性幹細胞から膵臓内分泌細胞膵臓内分泌細胞への分化のための、空気−液体界面での、ヒト胚性幹細胞の培養 |
EP4039798A1 (en) | 2012-12-31 | 2022-08-10 | Janssen Biotech, Inc. | Suspension and clustering of human pluripotent cells |
EP2756754B1 (de) | 2013-01-17 | 2017-01-04 | Vita 34 Ag | Verfahren zur Behandlung von Nabelschnurgewebe, insbesondere im Zusammenhang mit der Konservierung des Gewebes |
US20140212390A1 (en) * | 2013-01-30 | 2014-07-31 | NuTech Medical, Inc. | Placental Membrane Preparation and Methods of Making and Using Same |
US9763983B2 (en) | 2013-02-05 | 2017-09-19 | Anthrogenesis Corporation | Natural killer cells from placenta |
US9867939B2 (en) | 2013-03-12 | 2018-01-16 | Allergan, Inc. | Adipose tissue combinations, devices, and uses thereof |
AU2014248873B2 (en) | 2013-03-13 | 2017-03-23 | Allosource | Fascia fibrous compositions and methods for their use and manufacture |
DK2970883T3 (da) | 2013-03-14 | 2021-08-09 | Celularity Inc | Forbedrede placenta stamceller og bruge deraf |
CA2899713C (en) | 2013-03-15 | 2022-07-19 | Allosource | Cell repopulated collagen matrix for soft tissue repair and regeneration |
RU2539750C2 (ru) * | 2013-04-09 | 2015-01-27 | Федеральное государственное бюджетное образовательное учреждение высшего профессионального образования "Московский государственный университет имени М.В. Ломоносова" (МГУ) | Способ оценки иммуносупрессивных свойств мезенхимальных стромальных клеток человека |
US20140350516A1 (en) | 2013-05-23 | 2014-11-27 | Allergan, Inc. | Mechanical syringe accessory |
US11229789B2 (en) | 2013-05-30 | 2022-01-25 | Neurostim Oab, Inc. | Neuro activator with controller |
JP2016523125A (ja) | 2013-05-30 | 2016-08-08 | グラハム エイチ. クリーシー | 局所神経性刺激 |
US10058572B2 (en) | 2013-08-15 | 2018-08-28 | The Regents Of The University Of California | Placenta-derived multipotent stem cells |
US9248384B2 (en) | 2013-10-02 | 2016-02-02 | Allergan, Inc. | Fat processing system |
WO2015073913A1 (en) | 2013-11-16 | 2015-05-21 | Terumo Bct, Inc. | Expanding cells in a bioreactor |
EP3076982B1 (en) | 2013-12-06 | 2020-02-19 | Allosource | Method of drying sheets of tissue |
GB2536174B (en) * | 2013-12-17 | 2020-12-16 | Dtherapeutics Llc | Devices, systems and methods for tissue engineering of luminal grafts |
WO2015116735A1 (en) | 2014-01-28 | 2015-08-06 | Mayo Foundation For Medical Education And Research | Methods and combinations for killing senescent cells and for treating senescence-associated diseases and disorders |
US10328058B2 (en) | 2014-01-28 | 2019-06-25 | Mayo Foundation For Medical Education And Research | Treating atherosclerosis by removing senescent foam cell macrophages from atherosclerotic plaques |
US9993472B2 (en) | 2014-01-28 | 2018-06-12 | Unity Biotechnology, Inc. | Treatment for osteoarthritis in a joint by administering a means for inhibiting MDM2 |
EP3797742A1 (en) | 2014-02-12 | 2021-03-31 | Gyroscope Therapeutics Limited | Apparatus for suprachoroidal administration of therapeutic agent |
US10369237B2 (en) | 2014-03-10 | 2019-08-06 | 3-D Matrix, Ltd. | Sterilization and filtration of peptide compositions |
EP3116896B1 (en) | 2014-03-10 | 2018-12-19 | 3-D Matrix Ltd. | Self-assembling peptide compositions |
WO2015148704A1 (en) | 2014-03-25 | 2015-10-01 | Terumo Bct, Inc. | Passive replacement of media |
EP3139935A4 (en) * | 2014-05-07 | 2017-11-15 | Osiris Therapeutics, Inc. | Therapeutic placental compositions, methods of making and methods of use |
EP3140417B1 (en) * | 2014-05-09 | 2021-04-21 | Reelabs Private Limited | Foetal polymix of mesenchymal stem cells under hypoxic conditions for the treatment of clinical disorders |
US10029048B2 (en) | 2014-05-13 | 2018-07-24 | Allergan, Inc. | High force injection devices |
CA2949056A1 (en) | 2014-05-16 | 2015-11-19 | Janssen Biotech, Inc. | Use of small molecules to enhance mafa expression in pancreatic endocrine cells |
TW201603818A (zh) | 2014-06-03 | 2016-02-01 | 組織科技股份有限公司 | 組成物及方法 |
US9949874B2 (en) | 2014-06-06 | 2018-04-24 | Janssen Biotech, Inc. | Therapeutic agent delivery device with convergent lumen |
US9925088B2 (en) | 2014-06-06 | 2018-03-27 | Janssen Biotech, Inc. | Sub-retinal tangential needle catheter guide and introducer |
US20160000550A1 (en) * | 2014-07-05 | 2016-01-07 | Deborah Nagle | Methods for treating diseases of the colon |
CN106661552B (zh) * | 2014-07-11 | 2020-07-07 | 玛土撤拉有限公司 | 心脏细胞培养材料 |
US10322028B2 (en) | 2014-09-11 | 2019-06-18 | Orbit Biomedical Limited | Method and apparatus for sensing position between layers of an eye |
US10219936B2 (en) | 2014-09-11 | 2019-03-05 | Orbit Biomedical Limited | Therapeutic agent delivery device with advanceable cannula and needle |
US10064752B2 (en) | 2014-09-11 | 2018-09-04 | Orbit Biomedical Limited | Motorized suprachoroidal injection of therapeutic agent |
US10258502B2 (en) | 2014-09-18 | 2019-04-16 | Orbit Biomedical Limited | Therapeutic agent delivery device |
US9504905B2 (en) | 2014-09-19 | 2016-11-29 | Bally Gaming, Inc. | Card shuffling device and calibration method |
KR101613478B1 (ko) * | 2014-09-22 | 2016-04-19 | (주)안트로젠 | 중간엽줄기세포-하이드로겔을 함유하는 조성물 및 이의 제조방법 |
CN106715676A (zh) | 2014-09-26 | 2017-05-24 | 泰尔茂比司特公司 | 按计划供养 |
US11357799B2 (en) | 2014-10-03 | 2022-06-14 | Cedars-Sinai Medical Center | Cardiosphere-derived cells and exosomes secreted by such cells in the treatment of muscular dystrophy |
MX2017004520A (es) | 2014-10-14 | 2018-03-15 | Lynch Samuel | Composiciones para tratar heridas. |
WO2016068616A1 (ko) * | 2014-10-29 | 2016-05-06 | 차의과학대학교 산학협력단 | C3 또는 c1r 보체를 분비하는 태반 유래 세포 및 이를 포함하는 조성물 |
CA2966431C (en) * | 2014-10-31 | 2023-02-14 | The Administrators Of The Tulane Educational Fund | Surgical grafts for replacing the nipple and areola or damaged epidermis |
EP3189828B1 (en) | 2014-11-07 | 2020-07-29 | Exostemtech Co., Ltd. | Composition for differentiation induction of adipocyte containing stem cell-derived exosome, regeneration of adipose tissue, and skin whitening or wrinkle improvement |
CN106471371B (zh) * | 2014-12-05 | 2018-05-04 | 宣捷生物科技股份有限公司 | 区别间充质干细胞的方法 |
WO2016090215A2 (en) * | 2014-12-05 | 2016-06-09 | Janssen Biotech, Inc. | Treatment of ocular conditions using progenitor cells |
BR112017012581A2 (pt) * | 2014-12-16 | 2017-12-26 | Janssen Biotech Inc | tratamento de degeneração da retina com o uso de células progenitoras |
US20170080033A1 (en) * | 2014-12-16 | 2017-03-23 | Janssen Biotech, Inc. | Treatment of retinal degeneration using progenitor cells |
JP6800854B2 (ja) | 2014-12-19 | 2020-12-16 | ヤンセン バイオテツク,インコーポレーテツド | 多能性幹細胞の懸濁培養 |
US10342830B2 (en) | 2015-01-05 | 2019-07-09 | Gary M. Petrucci | Methods and materials for treating lung disorders |
WO2016126122A2 (ko) * | 2015-02-04 | 2016-08-11 | 한양대학교 에리카산학협력단 | 연골세포로 분화되고 있는 줄기세포로부터 추출된 엑소좀을 포함하는 연골세포 분화 유도 또는 연골조직 재생용 조성물 |
US11077301B2 (en) | 2015-02-21 | 2021-08-03 | NeurostimOAB, Inc. | Topical nerve stimulator and sensor for bladder control |
US20160243288A1 (en) | 2015-02-23 | 2016-08-25 | Tissuetech, Inc. | Apparatuses and methods for treating ophthalmic diseases and disorders |
CA2976544A1 (en) | 2015-03-10 | 2016-09-15 | Allergan Pharmaceuticals Holdings (Ireland) Unlimited Company | Multiple needle injector |
CA2979293C (en) | 2015-03-11 | 2022-01-04 | Timothy J. Kieffer | Pancreatic endocrine progenitor cell therapies for the treatment of obesity and type 2 diabetes (t2d) |
US11027047B2 (en) | 2015-03-31 | 2021-06-08 | The University Of North Carolina At Chapel Hill | Delivery vehicles for stem cells and uses thereof |
US10286009B2 (en) * | 2015-05-16 | 2019-05-14 | Asterias Biotherapeutics, Inc. | Pluripotent stem cell-derived oligodendrocyte progenitor cells for the treatment of spinal cord injury |
CN107847526A (zh) | 2015-05-20 | 2018-03-27 | 组织技术公司 | 用于预防上皮细胞的增殖和上皮‑间充质转换的组合物和方法 |
US10531957B2 (en) | 2015-05-21 | 2020-01-14 | Musculoskeletal Transplant Foundation | Modified demineralized cortical bone fibers |
US10335435B2 (en) | 2015-05-22 | 2019-07-02 | Marco Merida | Method for endoscopically delivering stem cells to the brain using an intranasal, injectable approach |
WO2017004592A1 (en) | 2015-07-02 | 2017-01-05 | Terumo Bct, Inc. | Cell growth with mechanical stimuli |
US10384207B2 (en) | 2015-07-21 | 2019-08-20 | Neuro Probe Incorporated | Assay apparatus and methods |
WO2017019822A1 (en) * | 2015-07-29 | 2017-02-02 | Medivation Technologies, Inc. | Pellet composition containing repair cells |
WO2017019832A1 (en) | 2015-07-29 | 2017-02-02 | Medivation Technologies, Inc. | Methods and compositions using repair cells and cationic dyes |
EP3342858B1 (en) | 2015-08-28 | 2023-10-04 | Rohto Pharmaceutical Co., Ltd. | Ror1-positive mesenchymal stem cells and method for preparing same, pharmaceutical composition containing ror1-positive mesenchymal stem cells and method for preparing same, and method for preventing or treating diseases by using ror1-positive mesenchymal stem cells |
USD797290S1 (en) | 2015-10-19 | 2017-09-12 | Spinal Surgical Strategies, Llc | Bone graft delivery tool |
WO2017087759A1 (en) | 2015-11-18 | 2017-05-26 | President And Fellows Of Harvard College | Cartridge-based system for long term culture of cell clusters |
US20170157179A1 (en) * | 2015-12-04 | 2017-06-08 | Janssen Biotech, Inc. | Treatment of retinal degeneration using progenitor cells |
KR20170076484A (ko) * | 2015-12-24 | 2017-07-04 | 삼성전자주식회사 | 프로토카데린의 과발현을 이용한 노화 세포를 분리하는 방법 |
US10814038B2 (en) | 2016-01-06 | 2020-10-27 | 3-D Matrix, Ltd. | Combination compositions |
US11253551B2 (en) | 2016-01-11 | 2022-02-22 | Cedars-Sinai Medical Center | Cardiosphere-derived cells and exosomes secreted by such cells in the treatment of heart failure with preserved ejection fraction |
SG11201805533QA (en) | 2016-01-14 | 2018-07-30 | Depuy Synthes Products Inc | Composition and methods for cryopreservation of hutc |
TW201733600A (zh) | 2016-01-29 | 2017-10-01 | 帝聖工業公司 | 胎兒扶持組織物及使用方法 |
WO2017136557A1 (en) * | 2016-02-05 | 2017-08-10 | Petrucci Gary M | Methods and materials for treating nerve injuries and neurological disorders |
US11458224B2 (en) * | 2016-03-04 | 2022-10-04 | University of Pittsburgh—of the Commonwealth System of Higher Education | Ovarian-derived hydrogels for biomedical and biotechnology applications |
US10478553B2 (en) | 2016-03-09 | 2019-11-19 | Orbit Biomedical Limited | Apparatus for subretinal administration of therapeutic agent via a curved needle |
GB201604304D0 (en) | 2016-03-14 | 2016-04-27 | Tigenix S A U | Adipose tissue-derived stromal stem cells for use in treating refractory complex perianal fistulas in crohn's disease |
EP3223181B1 (en) * | 2016-03-24 | 2019-12-18 | Sofradim Production | System and method of generating a model and simulating an effect on a surgical repair site |
CN116121189A (zh) | 2016-03-30 | 2023-05-16 | 阿斯特利亚斯生物治疗股份公司 | 少突胶质细胞祖细胞组合物 |
AU2017246114B2 (en) | 2016-04-08 | 2022-03-17 | Allergan, Inc. | Aspiration and injection device |
MA45479A (fr) | 2016-04-14 | 2019-02-20 | Janssen Biotech Inc | Différenciation de cellules souches pluripotentes en cellules de l'endoderme de l'intestin moyen |
CN109104869B (zh) | 2016-04-27 | 2022-07-01 | 日本乐敦制药株式会社 | 表达细胞表面标记物的间充质干细胞、包含该间充质干细胞的药物组合物及其制备方法 |
US11351200B2 (en) | 2016-06-03 | 2022-06-07 | Cedars-Sinai Medical Center | CDC-derived exosomes for treatment of ventricular tachyarrythmias |
US11104874B2 (en) | 2016-06-07 | 2021-08-31 | Terumo Bct, Inc. | Coating a bioreactor |
US11685883B2 (en) | 2016-06-07 | 2023-06-27 | Terumo Bct, Inc. | Methods and systems for coating a cell growth surface |
US11000410B2 (en) | 2016-06-17 | 2021-05-11 | Gyroscope Therapeutics Limited | Guide apparatus for tangential entry into suprachoroidal space |
US10806629B2 (en) | 2016-06-17 | 2020-10-20 | Gyroscope Therapeutics Limited | Injection device for subretinal delivery of therapeutic agent |
US10646374B2 (en) | 2016-06-17 | 2020-05-12 | Orbit Biomedical Limited | Apparatus and method to form entry bleb for subretinal delivery of therapeutic agent |
MA45502A (fr) | 2016-06-21 | 2019-04-24 | Janssen Biotech Inc | Génération de cellules bêta fonctionnelles dérivées de cellules souches pluripotentes humaines ayant une respiration mitochondriale glucose-dépendante et une réponse en sécrétion d'insuline en deux phases |
AU2017292652B2 (en) | 2016-07-05 | 2022-03-24 | Lifecell Corporation | Tissue matrices incorporating multiple tissue types |
RU2019102933A (ru) | 2016-07-05 | 2020-08-05 | Янссен Байотек, Инк. | Лечение сосудистого заболевания сетчатки с использованием клеток-предшественников |
KR20190055088A (ko) * | 2016-08-19 | 2019-05-22 | 리젠티스 코퍼레이션 | 점막 조직의 조직 재구성을 위한 세포외 매트릭스 |
EP3405204A4 (en) * | 2016-08-26 | 2020-03-18 | Restem Llc | COMPOSITION AND METHOD FOR USING CORD STEM CELLS |
EP3515459A4 (en) | 2016-09-20 | 2020-08-05 | Cedars-Sinai Medical Center | CELLS DERIVED FROM CARDIOSPHERES AND THEIR EXTRACELLULAR VESICLES TO DELAY OR REVERSE AGING AND AGE-RELATED DISORDERS |
IL301474A (en) * | 2016-11-02 | 2023-05-01 | Axogen Corp | Dragonfly embroidery implants, methods for their preparation, and their use |
RU2644306C1 (ru) * | 2016-11-22 | 2018-02-08 | Общество с ограниченной ответственностью "ДЖИ-Групп" | Способ восстановления дефектов покровных тканей |
WO2018125851A1 (en) * | 2016-12-26 | 2018-07-05 | Michael Moeller | Systems and methods to isolate and expand stem cells from urine |
US11273072B2 (en) | 2017-01-13 | 2022-03-15 | Gyroscope Therapeutics Limited | Suprachoroidal injection device |
US10772986B2 (en) | 2017-01-26 | 2020-09-15 | Allosource | Fascia fibrous compositions and methods for their use and manufacture |
CN110418645A (zh) | 2017-03-08 | 2019-11-05 | 日本乐敦制药株式会社 | 含有ror1阳性的间充质干细胞的、用于预防或处置伴随纤维化的疾病的药物组合物、及其制备方法、以及使用ror1阳性的间充质干细胞的伴随纤维化的疾病的预防或处置方法 |
US11076984B2 (en) | 2017-03-13 | 2021-08-03 | Gyroscope Therapeutics Limited | Method of performing subretinal drainage and agent delivery |
WO2018170394A1 (en) * | 2017-03-17 | 2018-09-20 | Rutgers, The State University Of New Jersey | Compositions and methods for wound healing |
US10767164B2 (en) | 2017-03-30 | 2020-09-08 | The Research Foundation For The State University Of New York | Microenvironments for self-assembly of islet organoids from stem cells differentiation |
US11702634B2 (en) | 2017-03-31 | 2023-07-18 | Terumo Bct, Inc. | Expanding cells in a bioreactor |
US11624046B2 (en) | 2017-03-31 | 2023-04-11 | Terumo Bct, Inc. | Cell expansion |
SG10202111394XA (en) | 2017-04-13 | 2021-12-30 | Senti Biosciences Inc | Combinatorial cancer immunotherapy |
WO2018195210A1 (en) | 2017-04-19 | 2018-10-25 | Cedars-Sinai Medical Center | Methods and compositions for treating skeletal muscular dystrophy |
US10478531B2 (en) | 2017-06-22 | 2019-11-19 | Gary M. Petrucci | Methods and materials for treating blood vessels |
WO2019018545A1 (en) | 2017-07-18 | 2019-01-24 | The Research Foundation For The State University Of New York | BIOMARKERS OF INTRACRANIAL ANEVISM |
US10251917B1 (en) | 2017-09-19 | 2019-04-09 | Gary M. Petrucci | Methods and materials for treating tumors |
US11123375B2 (en) | 2017-10-18 | 2021-09-21 | Lifecell Corporation | Methods of treating tissue voids following removal of implantable infusion ports using adipose tissue products |
JP7297739B2 (ja) | 2017-10-18 | 2023-06-26 | ライフセル コーポレーション | 脂肪組織製品および製造方法 |
US11246994B2 (en) | 2017-10-19 | 2022-02-15 | Lifecell Corporation | Methods for introduction of flowable acellular tissue matrix products into a hand |
WO2019079672A1 (en) | 2017-10-19 | 2019-04-25 | Lifecell Corporation | ACELLULAR TISSUE MATRIX PRODUCTS FLUIDS AND METHODS OF PRODUCTION |
US11629318B2 (en) | 2017-10-20 | 2023-04-18 | President And Fellows Of Harvard College | Methods for producing mature adipocytes and methods of use thereof |
WO2019083995A1 (en) * | 2017-10-23 | 2019-05-02 | Cell Medicine, Inc. | MESENCHYMAL STEM CELL THERAPY OF LEIGH SYNDROME |
TW201932126A (zh) * | 2017-11-03 | 2019-08-16 | 美商健生生物科技公司 | 抑制血管生成之方法 |
JP2021510608A (ja) | 2017-11-07 | 2021-04-30 | ニューロスティム オーエービー インコーポレイテッド | 適応回路を有する非侵襲性神経アクティベーター |
EP3727351A4 (en) | 2017-12-20 | 2021-10-06 | Cedars-Sinai Medical Center | MODIFIED EXTRACELLULAR VESICLES FOR IMPROVED TISSUE DELIVERY |
US11285177B2 (en) | 2018-01-03 | 2022-03-29 | Globus Medical, Inc. | Allografts containing viable cells and methods thereof |
JP7391327B2 (ja) | 2018-01-12 | 2023-12-05 | 国立大学法人大阪大学 | 重層扁平上皮細胞の正常分化・成熟促進剤、上皮疾患治療剤及び重層扁平上皮細胞の正常分化・成熟促進方法 |
US20190218521A1 (en) * | 2018-01-18 | 2019-07-18 | Lorenzo Bracco | Culture medium of viruses for human vaccines have to consist of human cells from placenta and/or from umbilical cord of a fetus of the blood type 0 Rh- and of the mother of the blood type 0 Rh- (both, fetus and mother, must be of the blood type 0 Rh-) |
US20200360563A1 (en) * | 2018-01-30 | 2020-11-19 | University Of Georgia Research Foundation, Inc. | Methods for Vascular Construction and Products Therefrom |
CN108384752A (zh) * | 2018-02-13 | 2018-08-10 | 中国人民解放军第四五五医院 | 成软骨培养基及其在微分裂技术中膝关节软骨分化中的应用 |
JP2021526556A (ja) * | 2018-05-30 | 2021-10-07 | ダイレクト バイオロジクス エルエルシー | 成長因子および細胞外小胞を凍結または粉状にした、間葉系幹細胞(msc)の調製物を含む助剤、ならびにその使用方法 |
CN108961233A (zh) * | 2018-06-28 | 2018-12-07 | 华侨大学 | 一种聚晶金刚石复合片表面缺陷分类识别方法 |
SG11202103317XA (en) | 2018-10-17 | 2021-05-28 | Senti Biosciences Inc | Combinatorial cancer immunotherapy |
US11419898B2 (en) | 2018-10-17 | 2022-08-23 | Senti Biosciences, Inc. | Combinatorial cancer immunotherapy |
AU2020210757A1 (en) | 2019-01-23 | 2021-08-05 | Asterias Biotherapeutics, Inc. | Dorsally-derived oligodendrocyte progenitor cells from human pluripotent stem cells |
US11759355B1 (en) | 2019-02-26 | 2023-09-19 | Gyroscope Therapeutics Limited | Method of delivering leading blebs and agent to subretinal space |
KR102169924B1 (ko) * | 2019-03-26 | 2020-10-26 | 연세대학교 산학협력단 | 연골세포 분화 유도용 조성물 및 이의 용도 |
KR102167257B1 (ko) * | 2019-05-28 | 2020-10-19 | 부산대학교 산학협력단 | 토마티딘 처리를 통한 줄기세포의 성숙화된 심근세포로의 분화유도 촉진 방법 |
CA3142151A1 (en) | 2019-05-30 | 2020-12-03 | Lifecell Corporation | Biologic breast implant |
JP2022538419A (ja) | 2019-06-26 | 2022-09-02 | ニューロスティム テクノロジーズ エルエルシー | 適応回路を備えた非侵襲性神経活性化装置 |
CA3152505A1 (en) * | 2019-08-29 | 2021-03-04 | Ajinomoto Co., Inc. | Method for producing mesenchymal stem cells from living body-derived cell sample containing mesenchymal stem cells |
US20220330530A1 (en) * | 2019-09-13 | 2022-10-20 | The University Of North Carolina At Chapel Hill | Method of making human mouse xenografts |
EP4041260A4 (en) * | 2019-10-07 | 2023-11-01 | University of Utah Research Foundation | CHONDRogenic HUMAN MESENCHYMAL STEM CELL LAYERS |
US11771834B2 (en) | 2019-10-11 | 2023-10-03 | Gyroscope Therapeutics Limited | Dose clip assembly for syringe |
EP4017580A4 (en) | 2019-12-16 | 2023-09-06 | Neurostim Technologies LLC | NON-INVASIVE NERVE ACTIVATOR WITH AMPLIFIED CHARGE DISTRIBUTION |
CN111718410B (zh) * | 2020-06-05 | 2022-10-11 | 江南大学 | 一种制备卵黄免疫球蛋白的方法 |
JP6967308B1 (ja) | 2020-06-30 | 2021-11-17 | 国立大学法人高知大学 | 胎児付属物由来組織細胞培養上清を含む脳神経障害治療剤 |
WO2022046954A1 (en) * | 2020-08-25 | 2022-03-03 | Celularity Inc. | Appl cells improved placental-derived adherent cells and methods of their use |
EP4259053A1 (en) | 2020-12-22 | 2023-10-18 | Gyroscope Therapeutics Limited | Ocular cannula guide |
WO2022154474A1 (ko) * | 2021-01-12 | 2022-07-21 | (주)셀라토즈테라퓨틱스 | 신경 재생 활성을 가진 신경재생촉진세포의 스크리닝 방법 |
CN115068438B (zh) * | 2022-04-28 | 2023-09-22 | 浙江大学医学院附属邵逸夫医院 | 破骨细胞前体同源靶向的细胞膜纳米囊泡制备方法及应用 |
CN115044542B (zh) * | 2022-06-30 | 2023-09-26 | 上海市东方医院(同济大学附属东方医院) | Sj000291942在诱导间充质干细胞成骨分化方面的应用 |
WO2024024708A1 (ja) * | 2022-07-26 | 2024-02-01 | 国立大学法人大阪大学 | 軟骨修復用組成物及びその製造方法 |
WO2024052733A1 (en) | 2022-09-06 | 2024-03-14 | Gyroscope Therapeutics Limited | Apparatus for subretinal administration of therapeutic agent via dual-curved needle |
Family Cites Families (326)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US229971A (en) | 1880-07-13 | Ttornets | ||
US2324800A (en) * | 1941-08-14 | 1943-07-20 | Pfizer Charles & Co | Purification of riboflavin |
US2654735A (en) * | 1949-07-29 | 1953-10-06 | Us Vitamin Corp | Process for the production of derivatives of 9-polyhydroxyalkylisoalloxazines and products obtained |
US2864848A (en) | 1954-07-19 | 1958-12-16 | Ca Nat Research Council | Method of producing l-alpha-glycerylphosphorylcholine |
US2912332A (en) | 1958-02-27 | 1959-11-10 | Swift & Co | Stabilized thiamine composition and method of enriching food products |
US3665061A (en) | 1969-07-16 | 1972-05-23 | United States Banknote Corp | Process for producing collagen sponges |
JPS5651747B2 (ja) * | 1973-05-31 | 1981-12-08 | ||
CH635748A5 (fr) * | 1977-08-16 | 1983-04-29 | Cellorgan Laboratoires Sa | Procede d'obtention de cellules placentaires de brebis. |
US4216144A (en) * | 1977-10-20 | 1980-08-05 | Ashmead H H | Soluble iron proteinates |
JPS6040439B2 (ja) * | 1978-03-29 | 1985-09-11 | 大正製薬株式会社 | ヒドロコルチゾン誘導体 |
US4352883A (en) | 1979-03-28 | 1982-10-05 | Damon Corporation | Encapsulation of biological material |
US4393240A (en) | 1981-07-06 | 1983-07-12 | Stille John K | Optically active phosphines |
US4544516A (en) | 1982-07-28 | 1985-10-01 | Battelle Development Corporation | Collagen orientation |
US4465776A (en) * | 1982-09-27 | 1984-08-14 | Research Corporation | Monoclonal antibodies to vitamin B6 and immunoassay method |
US4657866A (en) | 1982-12-21 | 1987-04-14 | Sudhir Kumar | Serum-free, synthetic, completely chemically defined tissue culture media |
US4487865A (en) * | 1983-12-15 | 1984-12-11 | Biomatrix, Inc. | Polymeric articles modified with hyaluronate |
US4963489A (en) | 1987-04-14 | 1990-10-16 | Marrow-Tech, Inc. | Three-dimensional cell and tissue culture system |
US5266480A (en) * | 1986-04-18 | 1993-11-30 | Advanced Tissue Sciences, Inc. | Three-dimensional skin culture system |
US5902741A (en) | 1986-04-18 | 1999-05-11 | Advanced Tissue Sciences, Inc. | Three-dimensional cartilage cultures |
US5863531A (en) | 1986-04-18 | 1999-01-26 | Advanced Tissue Sciences, Inc. | In vitro preparation of tubular tissue structures by stromal cell culture on a three-dimensional framework |
US4925667A (en) * | 1986-05-27 | 1990-05-15 | Qmax Technology Group, Inc. | Substrate with particulate cosmetic |
CA1322262C (en) | 1987-06-26 | 1993-09-21 | Yoshito Ikada | Artificial skin |
NZ226750A (en) | 1987-10-29 | 1990-09-26 | Amrad Corp Ltd | Immortalisation of neural precursor cells by introducing a retrovirus vector containing a myc-oncogene |
US5004681B1 (en) * | 1987-11-12 | 2000-04-11 | Biocyte Corp | Preservation of fetal and neonatal hematopoietic stem and progenitor cells of the blood |
US5192553A (en) | 1987-11-12 | 1993-03-09 | Biocyte Corporation | Isolation and preservation of fetal and neonatal hematopoietic stem and progenitor cells of the blood and methods of therapeutic use |
US5162405A (en) * | 1987-12-24 | 1992-11-10 | Elf Atochem North America, Inc. | Single-functional and mixtures of multi-functional oligomeric performance additive compositions and their uses |
GB8803697D0 (en) | 1988-02-17 | 1988-03-16 | Deltanine Research Ltd | Clinical developments using amniotic membrane cells |
US4963439A (en) | 1988-04-19 | 1990-10-16 | Ube Industries, Ltd. | Continuous fiber-reinforced Al-Co alloy matrix composite |
US20030032178A1 (en) | 1988-08-04 | 2003-02-13 | Williams Robert Lindsay | In vitro propagation of embryonic stem cells |
US5618670A (en) * | 1988-08-26 | 1997-04-08 | The United States Of America As Represented By The Department Of Health & Human Services | Detection method for c-raf-1 genes |
US4925677A (en) | 1988-08-31 | 1990-05-15 | Theratech, Inc. | Biodegradable hydrogel matrices for the controlled release of pharmacologically active agents |
US5284766A (en) * | 1989-02-10 | 1994-02-08 | Kao Corporation | Bed material for cell culture |
JPH06104061B2 (ja) | 1989-02-10 | 1994-12-21 | 花王株式会社 | 細胞培養支持体材料 |
EP0385733B1 (en) * | 1989-02-27 | 1994-06-01 | Takasago International Corporation | Process for preparing optically active 6-t-butoxy-3,5-dihydroxyhexanoic esters |
FR2646438B1 (fr) | 1989-03-20 | 2007-11-02 | Pasteur Institut | Procede de remplacement specifique d'une copie d'un gene present dans le genome receveur par l'integration d'un gene different de celui ou se fait l'integration |
US5437994A (en) | 1989-06-15 | 1995-08-01 | Regents Of The University Of Michigan | Method for the ex vivo replication of stem cells, for the optimization of hematopoietic progenitor cell cultures, and for increasing the metabolism, GM-CSF secretion and/or IL-6 secretion of human stromal cells |
US5574205A (en) | 1989-07-25 | 1996-11-12 | Cell Genesys | Homologous recombination for universal donor cells and chimeric mammalian hosts |
US5840580A (en) * | 1990-05-01 | 1998-11-24 | Becton Dickinson And Company | Phenotypic characterization of the hematopoietic stem cell |
US5145770A (en) * | 1990-06-04 | 1992-09-08 | Biosurface Technology, Inc. | Cryopreservation of cultured epithelial sheets |
US5612205A (en) | 1990-08-29 | 1997-03-18 | Genpharm International, Incorporated | Homologous recombination in mammalian cells |
US5336616A (en) * | 1990-09-12 | 1994-08-09 | Lifecell Corporation | Method for processing and preserving collagen-based tissues for transplantation |
US5342761A (en) | 1990-10-01 | 1994-08-30 | Research Development Foundation | Oncofetal gene, gene product and uses therefor |
US5506134A (en) | 1990-10-22 | 1996-04-09 | Corvas International, Inc. | Hypridoma and monoclonal antibody which inhibits blood coagulation tissue factor/factor VIIa complex |
US5486359A (en) | 1990-11-16 | 1996-01-23 | Osiris Therapeutics, Inc. | Human mesenchymal stem cells |
US5811094A (en) | 1990-11-16 | 1998-09-22 | Osiris Therapeutics, Inc. | Connective tissue regeneration using human mesenchymal stem cell preparations |
US5140100A (en) * | 1990-12-28 | 1992-08-18 | Cedars-Sinai Medical Center | Protein that inhibits production of human choriogonadotropin |
US5286632A (en) * | 1991-01-09 | 1994-02-15 | Jones Douglas H | Method for in vivo recombination and mutagenesis |
NL9100038A (nl) * | 1991-01-11 | 1992-08-03 | Stamicarbon | Enzym-gekatalyseerde bereiding van optisch aktieve carbonzuren. |
CZ232593A3 (en) | 1991-05-02 | 1994-07-13 | Yeda Res & Dev | Pharmaceutical preparation for preventing and/or therapy of pathological states |
US6399369B1 (en) | 1991-07-08 | 2002-06-04 | Neurospheres Holdings Ltd. | Multipotent neural stem cell cDNA libraries |
WO1993003139A1 (en) | 1991-08-08 | 1993-02-18 | Kao Corporation | Cell culture support, production thereof, and production of cell cluster using same |
EP0529751A1 (en) | 1991-08-09 | 1993-03-03 | W.R. Grace & Co.-Conn. | Cell culture substrate, test material for cell culture and preparations thereof |
AU2515992A (en) | 1991-08-20 | 1993-03-16 | Genpharm International, Inc. | Gene targeting in animal cells using isogenic dna constructs |
AU2694592A (en) * | 1991-09-30 | 1993-05-03 | Walser, Mackenzie | Methods for treatment of free-radical-mediated tissue injury |
US5308763A (en) * | 1991-10-01 | 1994-05-03 | The Johns Hopkins University | Method of making primary culture of olfactory neurons |
US5914265A (en) * | 1992-04-30 | 1999-06-22 | Baylor College Of Medicine | Keratin K1 expression vectors and methods of use |
WO1994000484A1 (en) | 1992-06-22 | 1994-01-06 | Young Henry E | Scar inhibitory factor and use thereof |
US5320962A (en) * | 1992-07-22 | 1994-06-14 | Duke University | DNA encoding the human A1 adenosine receptor |
US5589376A (en) | 1992-07-27 | 1996-12-31 | California Institute Of Technology | Mammalian neural crest stem cells |
US5356807A (en) * | 1992-09-08 | 1994-10-18 | Cornell Research Foundation | Cultured cell line of adult diploid cells from human brain and meningeal tissue |
US20040224409A1 (en) | 1992-09-25 | 2004-11-11 | Laurent Pradier | Recombinant adenoviruses coding for brain-derived neurotrophic factor (BDNF) |
ATE250138T1 (de) | 1992-10-29 | 2003-10-15 | Univ Australian | Angiogenese-inhibierende antikörper |
US5955343A (en) | 1992-12-28 | 1999-09-21 | Massachusetts Institute Of Technology | Stable macroscopic membranes formed by self-assembly of amphiphilic peptides and uses therefor |
US5670483A (en) * | 1992-12-28 | 1997-09-23 | Massachusetts Insititute Of Technology | Stable macroscopic membranes formed by self-assembly of amphiphilic peptides and uses therefor |
US5707643A (en) * | 1993-02-26 | 1998-01-13 | Santen Pharmaceutical Co., Ltd. | Biodegradable scleral plug |
US5494899A (en) * | 1993-04-07 | 1996-02-27 | Oklahoma Medical Research Foundation | Selective regulation of B lymphocyte precursors by hormones |
WO1994025584A1 (en) | 1993-04-28 | 1994-11-10 | Johns Hopkins University School Of Medicine | Chronic endothelial cell culture under flow |
IL110589A0 (en) | 1993-08-10 | 1994-11-11 | Bioph Biotech Entw Pharm Gmbh | Growth/differentiation factor of the TGF- beta family |
JP3680114B2 (ja) | 1993-09-17 | 2005-08-10 | 敏一 中村 | 脳神経障害治療剤 |
US6686198B1 (en) | 1993-10-14 | 2004-02-03 | President And Fellows Of Harvard College | Method of inducing and maintaining neuronal cells |
US6432711B1 (en) | 1993-11-03 | 2002-08-13 | Diacrin, Inc. | Embryonic stem cells capable of differentiating into desired cell lines |
US5456835A (en) * | 1993-11-08 | 1995-10-10 | Hemasure, Inc. | Device and process for removing free hemoglobin from blood |
DE4406073A1 (de) | 1994-02-24 | 1995-08-31 | Univ Ludwigs Albert | Verfahren zur Herstellung von humanen, klonogenen Fibroblasten, Verfahren zur Gentransfizierung von Fibroblasten und so erhaltene Fibroblasten |
US5698518A (en) | 1994-03-30 | 1997-12-16 | Oklahoma Medical Research Foundation | Method for regulating inflammation and tumor growth with calmodulin, calmodulin analogues or calmodulin antagonists |
US5466233A (en) | 1994-04-25 | 1995-11-14 | Escalon Ophthalmics, Inc. | Tack for intraocular drug delivery and method for inserting and removing same |
US6001647A (en) | 1994-04-28 | 1999-12-14 | Ixion Biotechnology, Inc. | In vitro growth of functional islets of Langerhans and in vivo uses thereof |
US5834308A (en) | 1994-04-28 | 1998-11-10 | University Of Florida Research Foundation, Inc. | In vitro growth of functional islets of Langerhans |
US6703017B1 (en) | 1994-04-28 | 2004-03-09 | Ixion Biotechnology, Inc. | Reversal of insulin-dependent diabetes by islet-producing stem cells, islet progenitor cells and islet-like structures |
PT952792E (pt) | 1994-06-06 | 2003-12-31 | Osiris Therapeutics Inc | Biomatriz para regeneracao dos tecidos |
IL114397A0 (en) | 1994-07-01 | 1995-10-31 | Bioph Biotech Entw Pharm Gmbh | Growth/differentiation factor of the TGF-beta-family |
US5935849A (en) * | 1994-07-20 | 1999-08-10 | Cytotherapeutics, Inc. | Methods and compositions of growth control for cells encapsulated within bioartificial organs |
US6309853B1 (en) | 1994-08-17 | 2001-10-30 | The Rockfeller University | Modulators of body weight, corresponding nucleic acids and proteins, and diagnostic and therapeutic uses thereof |
US5660982A (en) * | 1994-10-04 | 1997-08-26 | Tryggvason; Karl | Laminin chains: diagnostic uses |
US5789147A (en) | 1994-12-05 | 1998-08-04 | New York Blood Center, Inc. | Method for concentrating white cells from whole blood by adding a red cell sedimentation reagent to whole anticoagulated blood |
US5725493A (en) | 1994-12-12 | 1998-03-10 | Avery; Robert Logan | Intravitreal medicine delivery |
US5684032A (en) | 1994-12-13 | 1997-11-04 | Smithkline Beecham Corporation | Compounds |
US5843780A (en) * | 1995-01-20 | 1998-12-01 | Wisconsin Alumni Research Foundation | Primate embryonic stem cells |
US5736396A (en) | 1995-01-24 | 1998-04-07 | Case Western Reserve University | Lineage-directed induction of human mesenchymal stem cell differentiation |
US5906934A (en) * | 1995-03-14 | 1999-05-25 | Morphogen Pharmaceuticals, Inc. | Mesenchymal stem cells for cartilage repair |
US5718922A (en) * | 1995-05-31 | 1998-02-17 | Schepens Eye Research Institute, Inc. | Intravitreal microsphere drug delivery and method of preparation |
US5869079A (en) | 1995-06-02 | 1999-02-09 | Oculex Pharmaceuticals, Inc. | Formulation for controlled release of drugs by combining hydrophilic and hydrophobic agents |
US5693332C1 (en) | 1995-08-11 | 2001-01-09 | Univ California | Human keratinocytes supported on a hydrophilic membrane and methods of using same to effect wound closure |
US5641750A (en) | 1995-11-29 | 1997-06-24 | Amgen Inc. | Methods for treating photoreceptors using glial cell line-derived neurotrophic factor (GDNF) protein product |
US6200606B1 (en) | 1996-01-16 | 2001-03-13 | Depuy Orthopaedics, Inc. | Isolation of precursor cells from hematopoietic and nonhematopoietic tissues and their use in vivo bone and cartilage regeneration |
US5842477A (en) | 1996-02-21 | 1998-12-01 | Advanced Tissue Sciences, Inc. | Method for repairing cartilage |
CA2248549A1 (en) | 1996-03-15 | 1997-09-18 | Munin Corporation | Extracellular matrix signalling molecules |
US6223188B1 (en) * | 1996-04-10 | 2001-04-24 | Sun Microsystems, Inc. | Presentation of link information as an aid to hypermedia navigation |
JP2000508922A (ja) | 1996-04-26 | 2000-07-18 | ケース ウエスターン リザーブ ユニバーシティ | 間葉幹細胞を用いる皮膚再生 |
US6358737B1 (en) * | 1996-07-31 | 2002-03-19 | Board Of Regents, The University Of Texas System | Osteocyte cell lines |
US6787355B1 (en) * | 1996-08-26 | 2004-09-07 | Mcgill University | Multipotent neural stem cells from peripheral tissues and uses thereof |
US5919702A (en) | 1996-10-23 | 1999-07-06 | Advanced Tissue Science, Inc. | Production of cartilage tissue using cells isolated from Wharton's jelly |
WO1998031316A1 (en) * | 1997-01-17 | 1998-07-23 | Celadon Science, Llc | Methods for promoting healing of corneal resurfacing wounds |
WO1998033515A1 (en) | 1997-02-05 | 1998-08-06 | Case Western Reserve University | STIMULATORY EFFECTS OF bFGF AND BMP-2 ON OSTEOGENIC DIFFERENTIATION OF MESENCHYMAL STEM CELLS |
AU7481098A (en) | 1997-05-13 | 1998-12-08 | Case Western Reserve University | Osteoarthritis cartilage regeneration using human mesenchymal stem ce lls |
JP2002513383A (ja) | 1997-05-21 | 2002-05-08 | スローン−ケタリング・インスティテュート・フォー・キャンサー・リサーチ | 患者の脳組織でのアスコルビン酸の濃度を増加させる方法 |
AU738334B2 (en) * | 1997-05-30 | 2001-09-13 | Osteobiologics, Inc. | Fiber-reinforced, porous, biodegradable implant device |
ATE307195T1 (de) * | 1997-07-14 | 2005-11-15 | Osiris Therapeutics Inc | Herzmuskelregenerierung unter verwendung mesenchymaler stammzellen |
US5902598A (en) * | 1997-08-28 | 1999-05-11 | Control Delivery Systems, Inc. | Sustained release drug delivery devices |
CN100529063C (zh) * | 1997-12-02 | 2009-08-19 | 泽恩比奥公司 | 使脂肪基质细胞分化为成骨细胞的方法 |
US6059968A (en) * | 1998-01-20 | 2000-05-09 | Baxter International Inc. | Systems for processing and storing placenta/umbilical cord blood |
US6291240B1 (en) * | 1998-01-29 | 2001-09-18 | Advanced Tissue Sciences, Inc. | Cells or tissues with increased protein factors and methods of making and using same |
WO1999046366A1 (en) | 1998-03-13 | 1999-09-16 | Osiris Therapeutics, Inc. | Uses for humane non-autologous mesenchymal stem cells |
EP1076563B1 (en) | 1998-03-16 | 2005-05-11 | Cytovia, Inc. | Dipeptide caspase inhibitors and the use thereof |
US6179872B1 (en) * | 1998-03-17 | 2001-01-30 | Tissue Engineering | Biopolymer matt for use in tissue repair and reconstruction |
US6171610B1 (en) | 1998-04-24 | 2001-01-09 | University Of Massachusetts | Guided development and support of hydrogel-cell compositions |
AU3888699A (en) | 1998-05-07 | 1999-11-23 | University Of South Florida | Bone marrow cells as a source of neurons for brain and spinal cord repair |
ATE368731T1 (de) | 1998-05-29 | 2007-08-15 | Osiris Therapeutics Inc | Menschliche cd45+ und/oder fibroblasten+ mesenchymale stammzellen |
US6323188B1 (en) | 1998-07-01 | 2001-11-27 | Donald L. Weissman | Treatment and prevention of cardiovascular diseases, heart attack, and stroke, primary and subsequent, with help of aspirin and certain vitamins |
DE19833340A1 (de) | 1998-07-24 | 2000-02-10 | Karlsruhe Forschzent | Wurmförmiger Arbeitsmechanismus |
US20040037818A1 (en) | 1998-07-30 | 2004-02-26 | Brand Stephen J. | Treatment for diabetes |
EP2028269B1 (en) | 1998-08-10 | 2015-10-21 | THE GOVERNMENT OF THE UNITED STATES OF AMERICA, as represented by THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES | Differentiation of non-insulin producing cells into insulin producing cells by GLP-1 or Exendin-4 and uses thereof |
US5958767A (en) | 1998-08-14 | 1999-09-28 | The Children's Medical Center Corp. | Engraftable human neural stem cells |
US6284245B1 (en) | 1998-08-25 | 2001-09-04 | Diacrin, Inc. | Neural retinal cells and retinal pigment epithelium cells and their use in treatment of retinal disorders |
US6444205B2 (en) | 1998-09-30 | 2002-09-03 | Diacrin, Inc. | Transplantation of neural cells for the treatment of chronic pain or spasticity |
US6610540B1 (en) | 1998-11-18 | 2003-08-26 | California Institute Of Technology | Low oxygen culturing of central nervous system progenitor cells |
US6241369B1 (en) * | 1998-11-20 | 2001-06-05 | Cooper Technologies Company | Quick mount fixture |
US6144054A (en) * | 1998-12-04 | 2000-11-07 | International Business Machines Corporation | DRAM cell having an annular signal transfer region |
DE19856428C1 (de) * | 1998-12-08 | 2000-05-04 | Heraeus Noblelight Gmbh | Entladungslampe |
PT1144026E (pt) | 1998-12-24 | 2004-12-31 | Biosafe Sa | Sistema para separacao sanguinea util, em particular, para concentracoes de celulas estaminais hematopoieticas |
JP4932069B2 (ja) | 1999-01-25 | 2012-05-16 | 株式会社セルシード | アクリルアミド誘導体および該誘導体を含む重合体 |
MXPA01007810A (es) | 1999-02-04 | 2003-06-04 | Univ Mcgill | Plataforma para la diferenciacion de celulas. |
AU780794B2 (en) | 1999-02-10 | 2005-04-14 | Es Cell International Pte Ltd | Pancreatic progenitor cells, methods and uses related thereto |
US6592623B1 (en) * | 1999-08-31 | 2003-07-15 | Virginia Commonwealth University Intellectual Property Foundation | Engineered muscle |
KR100968165B1 (ko) | 1999-03-10 | 2010-07-06 | 더 리전츠 오브 더 유니버시티 오브 캘리포니아 | 지방 유래 간세포 및 격자 |
US20030007954A1 (en) | 1999-04-12 | 2003-01-09 | Gail K. Naughton | Methods for using a three-dimensional stromal tissue to promote angiogenesis |
DE60026983T2 (de) | 1999-04-16 | 2007-01-25 | William Marsh Rice University, Houston | Funktionalisiertes polypropylenfumarat und polypropylenfumarat-coethylenglykol |
US6261600B1 (en) | 1999-04-30 | 2001-07-17 | Drugtech Corporation | Folic acid supplement |
US7371400B2 (en) | 2001-01-02 | 2008-05-13 | The General Hospital Corporation | Multilayer device for tissue engineering |
US6372494B1 (en) * | 1999-05-14 | 2002-04-16 | Advanced Tissue Sciences, Inc. | Methods of making conditioned cell culture medium compositions |
US6287340B1 (en) * | 1999-05-14 | 2001-09-11 | Trustees Of Tufts College | Bioengineered anterior cruciate ligament |
AU4860900A (en) | 1999-06-02 | 2000-12-18 | Lifebank Services, L.L.C. | Methods of isolation, cryopreservation, and therapeutic use of human amniotic epithelial cells |
US6329904B1 (en) * | 1999-06-11 | 2001-12-11 | Safety Through Cellular, Inc. | Apparatus and method for providing weather and other alerts |
AU5886000A (en) | 1999-06-25 | 2001-01-31 | Northwestern University | Compositions, kits, and methods for modulating survival and differentiation of multi-potential hematopoietic progenitor cells |
US6333029B1 (en) | 1999-06-30 | 2001-12-25 | Ethicon, Inc. | Porous tissue scaffoldings for the repair of regeneration of tissue |
US6355699B1 (en) | 1999-06-30 | 2002-03-12 | Ethicon, Inc. | Process for manufacturing biomedical foams |
US7838289B2 (en) | 2001-02-14 | 2010-11-23 | Abt Holding Company | Assay utilizing multipotent adult stem cells |
IL147990A0 (en) | 1999-08-05 | 2002-09-12 | Mcl Llc | Multipotent adult stem cells and methods for isolation |
US6555374B1 (en) * | 1999-08-19 | 2003-04-29 | Artecel Sciences, Inc. | Multiple mesodermal lineage differentiation potentials for adipose tissue-derived stromal cells and uses thereof |
US6429013B1 (en) | 1999-08-19 | 2002-08-06 | Artecel Science, Inc. | Use of adipose tissue-derived stromal cells for chondrocyte differentiation and cartilage repair |
JP2003509374A (ja) | 1999-09-14 | 2003-03-11 | チルドレンズ メディカル センター コーポレーション | 骨髄細胞を用いる筋ジストロフィーの治療方法 |
US6331313B1 (en) | 1999-10-22 | 2001-12-18 | Oculex Pharmaceticals, Inc. | Controlled-release biocompatible ocular drug delivery implant devices and methods |
US20030129745A1 (en) | 1999-10-28 | 2003-07-10 | Robl James M. | Gynogenetic or androgenetic production of pluripotent cells and cell lines, and use thereof to produce differentiated cells and tissues |
EP1099754A1 (en) | 1999-11-10 | 2001-05-16 | Universiteit Leiden | Mesenchymal stem cells and/or progenitor cells, their isolation and use |
CN100475953C (zh) | 1999-12-06 | 2009-04-08 | 通用医疗公司 | 胰腺干细胞 |
US20030082155A1 (en) | 1999-12-06 | 2003-05-01 | Habener Joel F. | Stem cells of the islets of langerhans and their use in treating diabetes mellitus |
US20020164307A1 (en) | 1999-12-06 | 2002-11-07 | Habener Joel F. | Stem cells of the islets of langerhans and their use in treating diabetes mellitus |
US7785882B2 (en) | 2000-01-18 | 2010-08-31 | Cornell Research Foundation, Inc. | Neuronal progenitor cells from hippocampal tissue and a method for isolating and purifying them |
US7544509B2 (en) | 2000-01-24 | 2009-06-09 | Mcgill University | Method for preparing stem cell preparations |
US6610535B1 (en) | 2000-02-10 | 2003-08-26 | Es Cell International Pte Ltd. | Progenitor cells and methods and uses related thereto |
AU3499801A (en) | 2000-02-11 | 2001-08-20 | Schepens Eye Res Inst | Isolation and transplantation of retinal stem cells |
WO2001059072A1 (en) | 2000-02-11 | 2001-08-16 | Philadelphia Health And Education Corporation | Differentiation of bone marrow cells into neuronal cells and uses therefor |
WO2001065934A2 (en) * | 2000-03-09 | 2001-09-13 | Lee Walters | Applications of immune system tolerance to treatment of various diseases |
EP1263930A4 (en) | 2000-03-09 | 2004-07-21 | Saneron Ccel Therapeutics Inc | BLOOD CELLS OF THE HUMAN UBILICAL CORD USED AS A SOURCE OF NEURAL TISSUE FOR REPAIRING THE BRAIN AND THE SPINAL CORD |
EP1264877B1 (en) | 2000-03-16 | 2013-10-02 | Cellseed Inc. | Cell cultivation-support material, method of cocultivation of cells and cocultivated cell sheet obtained therefrom |
US6436704B1 (en) | 2000-04-10 | 2002-08-20 | Raven Biotechnologies, Inc. | Human pancreatic epithelial progenitor cells and methods of isolation and use thereof |
US6673606B1 (en) | 2000-04-12 | 2004-01-06 | The Children's Hospital Of Philadelphia | Therapeutic uses for mesenchymal stromal cells |
US6375972B1 (en) * | 2000-04-26 | 2002-04-23 | Control Delivery Systems, Inc. | Sustained release drug delivery devices, methods of use, and methods of manufacturing thereof |
EP1318833A2 (en) | 2000-05-12 | 2003-06-18 | The University of Utah Research Foundation | Compositions and methods for cell dedifferentiation and tissue regeneration |
US8273570B2 (en) | 2000-05-16 | 2012-09-25 | Riken | Process of inducing differentiation of embryonic cell to cell expressing neural surface marker using OP9 or PA6 cells |
US7049072B2 (en) | 2000-06-05 | 2006-05-23 | University Of South Florida | Gene expression analysis of pluri-differentiated mesenchymal progenitor cells and methods for diagnosing a leukemic disease state |
US6759039B2 (en) | 2000-06-30 | 2004-07-06 | Amcyte, Inc. | Culturing pancreatic stem cells having a specified, intermediate stage of development |
WO2002010349A1 (en) | 2000-07-21 | 2002-02-07 | Cellseed Inc. | Cultured epidermal cell sheet, laminated cultured skin sheet and process for producing the same |
DE60143892D1 (de) * | 2000-07-21 | 2011-03-03 | Cellseed Ind | Herzmuskel-ähnliche zellschicht, dreidimensionales konstrukt, herzmuskel-ähnliches gewebe und verfahren zur herstellung |
US6984522B2 (en) | 2000-08-03 | 2006-01-10 | Regents Of The University Of Michigan | Isolation and use of solid tumor stem cells |
DE10038814A1 (de) * | 2000-08-09 | 2002-02-21 | Abb Research Ltd | Hochspannungs-Gleichstromwandler |
WO2002026941A2 (en) | 2000-09-29 | 2002-04-04 | Kooy Derek V D | Primitive neural stem cells and method for differentiation of stem cells to neural cells |
US6639470B1 (en) | 2000-10-06 | 2003-10-28 | Skyworks Solutions, Inc. | Constant current biasing circuit for linear power amplifiers |
US7560280B2 (en) | 2000-11-03 | 2009-07-14 | Kourion Therapeutics Gmbh | Human cord blood derived unrestricted somatic stem cells (USSC) |
AU2002230669A1 (en) | 2000-11-06 | 2002-05-15 | The Salk Institute For Biological Studies | Postmortem stem cells |
IL156234A0 (en) | 2000-11-30 | 2004-01-04 | Stemron Inc | Isolated homozygous stem cells, differentiated cells derived therefrom, and materials and methods for making and using same |
AU2002220209B2 (en) | 2000-12-06 | 2006-05-25 | Robert J. Hariri | Method of collecting placental stem cells |
US7311905B2 (en) | 2002-02-13 | 2007-12-25 | Anthrogenesis Corporation | Embryonic-like stem cells derived from post-partum mammalian placenta, and uses and methods of treatment using said cells |
US20030032179A1 (en) * | 2000-12-06 | 2003-02-13 | Hariri Robert J. | Post-partum mammalian placenta, its use and placental stem cells therefrom |
CA2365376C (en) | 2000-12-21 | 2006-03-28 | Ethicon, Inc. | Use of reinforced foam implants with enhanced integrity for soft tissue repair and regeneration |
US6599323B2 (en) | 2000-12-21 | 2003-07-29 | Ethicon, Inc. | Reinforced tissue implants and methods of manufacture and use |
EP1366148A2 (en) | 2001-01-24 | 2003-12-03 | THE GOVERNMENT OF THE UNITED STATES OF AMERICA, represented by THE DEPARTMENT OF HEALTH & HUMAN SERVICES | Differentiation of stem cells to pancreatic endocrine cells |
WO2002061053A1 (en) | 2001-01-31 | 2002-08-08 | The General Hospital Corporation | Renal stem cells and uses thereof |
US7449180B2 (en) | 2001-02-06 | 2008-11-11 | John Kisiday | Macroscopic scaffold containing amphiphilic peptides encapsulating cells |
DE60230593D1 (de) | 2001-02-06 | 2009-02-12 | Massachusetts Inst Technology | Peptidgerüstverkapselung von gewebszellen und verwendungen davon |
KR101012952B1 (ko) * | 2001-02-14 | 2011-02-08 | 안트로제네시스 코포레이션 | 산후 포유류의 태반, 이의 용도 및 태반 줄기세포 |
JP2005503120A (ja) * | 2001-03-27 | 2005-02-03 | マサチューセッツ インスティテュート オブ テクノロジー | Fgfダイマー化に関する方法及び生成物 |
US7838292B1 (en) | 2001-03-29 | 2010-11-23 | University Of Louisville Research Foundation, Inc. | Methods for obtaining adult human olfactory progenitor cells |
CA2442177A1 (en) | 2001-03-29 | 2002-10-10 | Ixion Biotechnology, Inc. | Method for transdifferentiation of non-pancreatic stem cells to the pancreatic differentiation pathway |
US20050054102A1 (en) | 2001-04-19 | 2005-03-10 | Anna Wobus | Method for differentiating stem cells into insulin-producing cells |
KR100762261B1 (ko) | 2001-04-27 | 2007-10-04 | (주)바이오니아 | 전장 상보 디옥시리보핵산 제조 방법과 이에 사용되는앵커와 프라이머 |
US20030211605A1 (en) | 2001-05-01 | 2003-11-13 | Lee Sang-Hun | Derivation of midbrain dopaminergic neurons from embryonic stem cells |
US20030022369A1 (en) * | 2001-05-18 | 2003-01-30 | Helen Fillmore | Differentiation of specialized dermal and epidermal cells into neuronal cells |
JP2005515753A (ja) | 2001-05-25 | 2005-06-02 | サイセラ,インコーポレイテッド | 幹細胞分化 |
EP1406573A4 (en) | 2001-06-07 | 2005-03-30 | Skinmedica Inc | CONDITIONED CELL CULTURE MEDIA AND ITS USES |
RU2183966C1 (ru) | 2001-07-06 | 2002-06-27 | Общество с ограниченной ответственностью "Сибларекс" | Состав биофлавоноидного комплекса сибларекс для биологически активных добавок, медицинских и химико-фармацевтических изделий и способ получения биофлавоноидного комплекса сибларекс для биологически активных добавок, медицинских и химико-фармацевтических изделий |
US6402263B1 (en) | 2001-07-24 | 2002-06-11 | Robert Bosch Corporation | Dual actuation master cylinder |
EP1423504B1 (en) * | 2001-08-08 | 2009-09-23 | Levesque Biosciences, Inc. | Compositions and methods for isolation, propagation, and differentiation of non-embryonic human stem cells and uses thereof |
US20030211603A1 (en) | 2001-08-14 | 2003-11-13 | Earp David J. | Reprogramming cells for enhanced differentiation capacity using pluripotent stem cells |
WO2003018767A2 (en) * | 2001-08-27 | 2003-03-06 | Advanced Cell Technology, Inc. | Trans-differentiation and re-differentiation of somatic cells and production of cells for cell therapies |
US20030104997A1 (en) | 2001-09-05 | 2003-06-05 | Black Ira B. | Multi-lineage directed induction of bone marrow stromal cell differentiation |
CN1195055C (zh) | 2001-09-06 | 2005-03-30 | 周胜利 | 从胎盘组织中提取造血干细胞用于建立造血干细胞库的新方法 |
US20050064587A1 (en) | 2001-09-07 | 2005-03-24 | Lawrence Rosenberg | Pancreatic small cells and uses thereof |
US9969980B2 (en) | 2001-09-21 | 2018-05-15 | Garnet Biotherapeutics | Cell populations which co-express CD49c and CD90 |
EP1298201A1 (en) | 2001-09-27 | 2003-04-02 | Cardion AG | Process for the production of cells exhibiting an islet-beta-cell-like state |
US7072332B2 (en) * | 2001-09-27 | 2006-07-04 | Samsung Electronics Co., Ltd. | Soft switch using distributed firewalls for load sharing voice-over-IP traffic in an IP network |
CA2461859A1 (en) | 2001-09-28 | 2003-04-10 | Es Cell International Pte Ltd | Methods of derivation and propagation of undifferentiated human embryonic stem (hes) cells on feeder-free matrices and human feeder layers |
EP1444345A4 (en) | 2001-10-18 | 2004-12-08 | Ixion Biotechnology Inc | TRANSFORMATION OF STEM CELLS AND LIVER PROGENITORS INTO FUNCTIONAL CELLS OF PANCREAS |
US7129034B2 (en) * | 2001-10-25 | 2006-10-31 | Cedars-Sinai Medical Center | Differentiation of whole bone marrow |
JP2005533480A (ja) | 2001-11-09 | 2005-11-10 | アーテセル・サイエンシズ・インコーポレーテツド | 脂肪組織由来間質細胞の膵内分泌分化およびその使用 |
US7491690B2 (en) | 2001-11-14 | 2009-02-17 | Northwestern University | Self-assembly and mineralization of peptide-amphiphile nanofibers |
AU2002363659B2 (en) * | 2001-11-15 | 2008-09-25 | Children's Medical Center Corporation | Methods of isolation, expansion and differentiation of fetal stem cells from chorionic villus, amniotic fluid, and placenta and therapeutic uses thereof |
JP3728750B2 (ja) * | 2001-11-22 | 2005-12-21 | ニプロ株式会社 | 培養皮膚及びその製造方法 |
CN1596130A (zh) | 2001-11-28 | 2005-03-16 | 安琪士多摩奇株式会社 | 治疗神经退行性疾病的基因治疗药物 |
US6712850B2 (en) | 2001-11-30 | 2004-03-30 | Ethicon, Inc. | Porous tissue scaffolds for the repair and regeneration of dermal tissue |
AU2002351238B2 (en) | 2001-12-04 | 2009-01-08 | Organogenesis Inc. | Cultured cells from pancreatic islets |
US20030109036A1 (en) * | 2001-12-06 | 2003-06-12 | The Regents Of The University Of California | Method for differentiating islet precursor cells into beta cells |
WO2003047607A1 (fr) * | 2001-12-06 | 2003-06-12 | Sankyo Company, Limited | Compositions medicales contenant des cellules amniotiques humaines |
KR101008868B1 (ko) | 2001-12-07 | 2011-01-17 | 제론 코포레이션 | 인간 배아 줄기세포 유래의 섬세포 |
US7166464B2 (en) * | 2001-12-11 | 2007-01-23 | Cytograft Tissue Engineering, Inc. | Method of culturing cells to produce a tissue sheet |
JP3934539B2 (ja) | 2001-12-12 | 2007-06-20 | 独立行政法人科学技術振興機構 | 胎盤等由来の成体又は生後組織の前駆細胞 |
US20030113910A1 (en) * | 2001-12-18 | 2003-06-19 | Mike Levanduski | Pluripotent stem cells derived without the use of embryos or fetal tissue |
WO2003055989A2 (en) * | 2001-12-21 | 2003-07-10 | Mount Sinai Hospital | Cellular compositions and methods of making and using them |
US7101546B2 (en) | 2001-12-21 | 2006-09-05 | Amcyte, Inc. | In situ maturation of cultured pancreatic stem cells having a specified, intermediate stage of development |
CA2471540A1 (en) | 2001-12-28 | 2003-07-10 | Cellartis Ab | A method for the establishment of a pluripotent human blastocyst-derived stem cell line |
JP2005514926A (ja) | 2002-01-14 | 2005-05-26 | ザ・ボード・オブ・トラスティーズ・オブ・ザ・ユニバーシティ・オブ・イリノイ | 新規ほ乳類多分化能幹細胞および組成物、その調製方法および投与方法 |
US20030158089A1 (en) * | 2002-01-24 | 2003-08-21 | Xenoport, Inc. | Administrative agents via the SMVT transporter |
US20030162290A1 (en) * | 2002-01-25 | 2003-08-28 | Kazutomo Inoue | Method for inducing differentiation of embryonic stem cells into functioning cells |
AU2003217357A1 (en) | 2002-02-07 | 2003-09-02 | The Research Foundation Of The State University Of New York | Generation of new insulin cells from progenitor cells present in adult pancreatic islets |
JP2005517402A (ja) | 2002-02-13 | 2005-06-16 | アンスロジェネシス コーポレーション | 分娩後の哺乳動物胎盤由来の胚様幹細胞、ならびに該細胞の用途および該細胞を用いる治療法 |
WO2003070189A2 (en) | 2002-02-15 | 2003-08-28 | Cornell Research Foundation, Inc. | Enhancing neurotrophin-induced neurogenesis by endogenous neural progenitor cells by concurrent overexpression of brain derived neurotrophic factor and an inhibitor of a pro-gliogenic bone morphogenetic protein |
US7371719B2 (en) | 2002-02-15 | 2008-05-13 | Northwestern University | Self-assembly of peptide-amphiphile nanofibers under physiological conditions |
EP1483371B1 (en) | 2002-02-19 | 2007-06-27 | Medipost, Co., Ltd. | Isolation and culture-expansion methods of mesenchymal stem/progenitor cells from umbilical cord blood, and differentiation method of umbilical cord blood-derived mesenchymal stem/progenitor cells into various mesenchymal tissues |
WO2003072728A2 (en) | 2002-02-22 | 2003-09-04 | University Of Florida | Cellular trans-differentiation |
US7736892B2 (en) | 2002-02-25 | 2010-06-15 | Kansas State University Research Foundation | Cultures, products and methods using umbilical cord matrix cells |
US20030161818A1 (en) * | 2002-02-25 | 2003-08-28 | Kansas State University Research Foundation | Cultures, products and methods using stem cells |
US7150990B2 (en) | 2002-03-06 | 2006-12-19 | Reprocell, Inc. | Self-renewing pluripotent hepatic stem cells |
JP2003259862A (ja) | 2002-03-12 | 2003-09-16 | Fuji Photo Film Co Ltd | 細胞培養担体 |
AU2003221173A1 (en) | 2002-03-27 | 2003-10-08 | Asahi Kasei Kabushiki Kaisha | Placenta-origin mesenchymal cells and medicinal use thereof |
US7498171B2 (en) * | 2002-04-12 | 2009-03-03 | Anthrogenesis Corporation | Modulation of stem and progenitor cell differentiation, assays, and uses thereof |
MXPA04009997A (es) | 2002-04-12 | 2004-12-13 | Celgene Corp | Modulacion de la diferenciacion de celulas madre y progenitoras, ensayos y usos de las mismas. |
JP4136434B2 (ja) | 2002-04-17 | 2008-08-20 | 進 清野 | インスリン産生細胞の誘導 |
US20040161419A1 (en) | 2002-04-19 | 2004-08-19 | Strom Stephen C. | Placental stem cells and uses thereof |
EP1497435A4 (en) | 2002-04-19 | 2005-07-27 | Univ Pittsburgh | PLACENTAL STEM CELLS AND USES |
AU2003239176A1 (en) | 2002-04-25 | 2003-11-10 | Wisconsin Alumni Research Foundation | Neurodegenerative disorder treatment using gdnf secreting neural cells |
US20040029269A1 (en) * | 2002-05-07 | 2004-02-12 | Goldman Steven A | Promoter-based isolation, purification, expansion, and transplantation of neuronal progenitor cells, oligodendrocyte progenitor cells, or neural stem cells from a population of embryonic stem cells |
US20040014662A1 (en) | 2002-05-08 | 2004-01-22 | Per Lindquist | Modulation of neural stem cells and neural progenitor cells |
AU2003228255A1 (en) | 2002-05-28 | 2003-12-19 | Becton, Dickinson And Company | Pancreatic acinar cells into insulin-producing cells |
JP2005528105A (ja) | 2002-05-30 | 2005-09-22 | セルジーン・コーポレーション | 細胞分化をモジュレートするため、並びに骨髄増殖性疾患及び骨髄異形成症候群を治療するためのjnk又はmkk阻害剤の使用方法 |
GB2405642B (en) | 2002-06-07 | 2007-03-28 | Es Cell Int Pte Ltd | Methods of regulating differentiation in stem cells |
WO2003104423A2 (en) * | 2002-06-11 | 2003-12-18 | Roy Ogle | Meningeal-derived stem cells |
WO2004003561A1 (en) | 2002-06-27 | 2004-01-08 | Northwestern University | Peptide rod amphiphiles and self-assembly of same |
US7285415B2 (en) | 2002-07-11 | 2007-10-23 | The Regents Of The University Of California | Oligodendrocytes derived from human embryonic stem cells for remyelination and treatment of spinal cord injury |
GB0216286D0 (en) | 2002-07-15 | 2002-08-21 | Univ Leeds | Network |
AU2003242976A1 (en) * | 2002-07-16 | 2004-02-02 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Methods of implanting mesenchymal stem cells for tissue repair and formation |
US7390659B2 (en) | 2002-07-16 | 2008-06-24 | The Trustees Of Columbia University In The City Of New York | Methods for inducing differentiation of embryonic stem cells and uses thereof |
CA2494040A1 (en) | 2002-07-29 | 2004-02-05 | Es Cell International Pte Ltd. | Multi-step method for the differentiation of insulin positive, glucose |
WO2004011012A2 (en) | 2002-07-29 | 2004-02-05 | Asahi Kasei Kabushiki Kaisha | Stem cells for treating pancreatic damage |
WO2004016747A2 (en) | 2002-08-14 | 2004-02-26 | University Of Florida | Bone marrow cell differentiation |
US20060128014A1 (en) * | 2002-08-26 | 2006-06-15 | Johan Haggblad | Compositions and methods for culturing stem cells |
WO2004020601A2 (en) * | 2002-08-28 | 2004-03-11 | University Of Florida | Neurogenesis from hepatic stem cells |
EP1539928A4 (en) | 2002-09-06 | 2006-09-06 | Amcyte Inc | POSIOTIVE PANCREATIC ENDOCRINE PROGENITOR CELLS CD56 IN ADULT HUMAN BEINGS |
US9969977B2 (en) | 2002-09-20 | 2018-05-15 | Garnet Biotherapeutics | Cell populations which co-express CD49c and CD90 |
US6766863B2 (en) * | 2002-09-20 | 2004-07-27 | Hypro Corporation | Fire fighting foam injection system with auto-start feature |
US20040062753A1 (en) | 2002-09-27 | 2004-04-01 | Alireza Rezania | Composite scaffolds seeded with mammalian cells |
JP4262465B2 (ja) * | 2002-10-24 | 2009-05-13 | 富士フイルム株式会社 | 細胞培養方法 |
WO2004039248A2 (en) | 2002-10-31 | 2004-05-13 | The General Hospital Corporation | Repairing or replacing tissues or organs |
WO2004052177A2 (en) | 2002-12-05 | 2004-06-24 | Case Western Reserve University | Cell-based therapies for ischemia |
JP4571387B2 (ja) | 2003-02-07 | 2010-10-27 | 宣男 櫻川 | ヒト羊膜由来サイドポピュレーション細胞及びその用途 |
WO2004072104A2 (en) | 2003-02-11 | 2004-08-26 | Northwestern University | Methods and materials for nanocrystalline surface coatings and attachment of peptide amphiphile nanofibers thereon |
JP4790592B2 (ja) | 2003-02-11 | 2011-10-12 | ダビース,ジヨン・イー | ヒト臍帯のウォートンジェリーからの前駆細胞 |
US7521481B2 (en) | 2003-02-27 | 2009-04-21 | Mclaurin Joanne | Methods of preventing, treating and diagnosing disorders of protein aggregation |
WO2006019366A1 (en) * | 2003-03-28 | 2006-02-23 | Wisconsin Alumni Research Foundation | Physiochemical culture conditions for embryonic stem cells |
US7960166B2 (en) | 2003-05-21 | 2011-06-14 | The General Hospital Corporation | Microfabricated compositions and processes for engineering tissues containing multiple cell types |
US7875272B2 (en) | 2003-06-27 | 2011-01-25 | Ethicon, Incorporated | Treatment of stroke and other acute neuraldegenerative disorders using postpartum derived cells |
US9572840B2 (en) | 2003-06-27 | 2017-02-21 | DePuy Synthes Products, Inc. | Regeneration and repair of neural tissue using postpartum-derived cells |
US8790637B2 (en) | 2003-06-27 | 2014-07-29 | DePuy Synthes Products, LLC | Repair and regeneration of ocular tissue using postpartum-derived cells |
EP1641913B1 (en) * | 2003-06-27 | 2016-01-06 | DePuy Synthes Products, Inc. | Postpartum cells derived from umbilical cord tissue, and methods of making and using the same |
AU2004269409A1 (en) | 2003-08-29 | 2005-03-10 | Regents Of The University Of Minnesota | Kidney derived stem cells and methods for their isolation, differentiation and use |
US20050089513A1 (en) | 2003-10-28 | 2005-04-28 | Norio Sakuragawa | Side population cells originated from human amnion and their uses |
EP2228035A1 (en) * | 2003-12-23 | 2010-09-15 | FMC Biopolymer AS | Use of alginate matrices to control cell growth |
TWI276685B (en) | 2003-12-30 | 2007-03-21 | Ind Tech Res Inst | Conditional medium for culturing Schwann cells |
US7534606B2 (en) | 2004-01-12 | 2009-05-19 | National Health Research Institutes | Placental stem cell and methods thereof |
DE102004043256B4 (de) | 2004-09-07 | 2013-09-19 | Rheinische Friedrich-Wilhelms-Universität Bonn | Skalierbarer Prozess zur Kultivierung undifferenzierter Stammzellen in Suspension |
US8039258B2 (en) | 2004-09-28 | 2011-10-18 | Ethicon, Inc. | Tissue-engineering scaffolds containing self-assembled-peptide hydrogels |
JP2008518597A (ja) | 2004-10-29 | 2008-06-05 | セントカー・インコーポレーテツド | 化学的規定培地組成物 |
US7655678B2 (en) * | 2004-11-30 | 2010-02-02 | Council of Scientfic & Industrial Research | Pharmaceutical composition for the management of tumors |
WO2006083394A2 (en) | 2004-12-21 | 2006-08-10 | Ethicon, Inc. | Postpartum cells derived from placental tissue, and methods of making, culturing, and using the same |
US20060153815A1 (en) * | 2004-12-21 | 2006-07-13 | Agnieszka Seyda | Tissue engineering devices for the repair and regeneration of tissue |
WO2006101548A2 (en) | 2004-12-21 | 2006-09-28 | Ethicon, Inc. | Postpartum cells derived from umbilical cord tissue, and methods of making, culturing, and using the same |
WO2006071777A2 (en) | 2004-12-23 | 2006-07-06 | Ethicon Incorporated | Soft tissue repair and regeneration using postpartum-derived cells and cell products |
CA2592435C (en) | 2004-12-23 | 2017-03-28 | Ethicon, Incorporated | Treatment of stroke and other acute neural degenerative disorders using postpartum derived cells |
PL1831356T3 (pl) | 2004-12-23 | 2017-07-31 | DePuy Synthes Products, Inc. | Komórki poporodowe pochodzące z tkanki pępowinowej i sposoby ich wytwarzania i stosowania |
EP1838842A2 (en) | 2004-12-23 | 2007-10-03 | Ethicon, Incorporated | Treatment of osteochondral diseases using postpartum-derived cells and products thereof |
US7741311B2 (en) | 2005-01-03 | 2010-06-22 | Shaker Mousa | Composition and method for treating occlusive vascular diseases, nerve regeneration, and wound healing |
JP2008538276A (ja) | 2005-01-28 | 2008-10-23 | ノヴァセラ・リミテッド | 胚幹細胞培養のための方法 |
EP2460875A1 (en) | 2005-03-31 | 2012-06-06 | Stemnion, Inc. | Amnion-derived cell compositions, methods of making and uses thereof |
US7923007B2 (en) | 2005-08-08 | 2011-04-12 | Academia Sinica | Brain tissue damage therapies |
PL1971681T3 (pl) * | 2005-12-16 | 2018-01-31 | Depuy Synthes Products Inc | Kompozycje oraz sposoby do hamowania niepożądanej odpowiedzi immunologicznej w przypadku transplantacji z brakiem zgodności tkankowej |
WO2007073552A1 (en) | 2005-12-19 | 2007-06-28 | Ethicon, Inc. | In vitro expansion of postpartum derived cells in roller bottles |
WO2007076522A2 (en) | 2005-12-28 | 2007-07-05 | Ethicon, Incorporated | Treatment of peripheral vascular disease using postpartum-derived cells |
US9125906B2 (en) | 2005-12-28 | 2015-09-08 | DePuy Synthes Products, Inc. | Treatment of peripheral vascular disease using umbilical cord tissue-derived cells |
KR20210122908A (ko) | 2005-12-29 | 2021-10-12 | 안트로제네시스 코포레이션 | 태반 줄기 세포 집단 |
JP5106416B2 (ja) * | 2006-01-06 | 2012-12-26 | アジレント・テクノロジーズ・インク | 濃縮(packed)DNAポリメラーゼを含む核酸複製のための反応緩衝液組成物 |
PT2548951E (pt) | 2006-03-23 | 2016-06-14 | Pluristem Ltd | Métodos para expansão celular e usos de células e de meios condicionados produzidos através deles para terapia |
WO2007146105A2 (en) * | 2006-06-05 | 2007-12-21 | Cryo-Cell International, Inc. | Procurement, isolation and cryopreservation of fetal placental cells |
WO2008045498A1 (en) * | 2006-10-12 | 2008-04-17 | Ethicon, Inc. | Kidney-derived cells and methods of use in tissue repair and regeneration |
ES2524443T3 (es) | 2006-11-13 | 2014-12-09 | DePuy Synthes Products, LLC | Expansión in vitro de células postparto usando microportadores |
DK2120977T3 (da) * | 2007-02-12 | 2013-08-12 | Anthrogenesis Corp | Behandling af inflammatoriske sygdomme under anvendelse af placenta-stamceller |
US20080305148A1 (en) | 2007-03-19 | 2008-12-11 | National Yang Ming University | Treatment of spinal injuries using human umbilical mesenchymal stem cells |
US8034329B2 (en) | 2007-10-05 | 2011-10-11 | Advanced Technologies And Regenerative Medicine, Llc | Repair and regeneration of renal tissue using human umbilical cord tissue-derived cells |
US20090123620A1 (en) * | 2007-11-14 | 2009-05-14 | Hiti Thomas R | Automated Application of an Antimycotic Composition to Sliced Foodstuffs and an Antimycotic Application Apparatus |
US8236538B2 (en) | 2007-12-20 | 2012-08-07 | Advanced Technologies And Regenerative Medicine, Llc | Methods for sterilizing materials containing biologically active agents |
WO2009086215A2 (en) | 2007-12-21 | 2009-07-09 | Wyeth | Pathway analysis of cell culture phenotypes and uses thereof |
ES2621610T3 (es) | 2007-12-27 | 2017-07-04 | DePuy Synthes Products, Inc. | Tratamiento de la degeneración de discos intervertebrales utilizando células derivadas de tejido cordón umbilical humano |
TWI363851B (en) * | 2008-03-28 | 2012-05-11 | Ind Tech Res Inst | Lighting device and assembling method thereof |
US10179900B2 (en) | 2008-12-19 | 2019-01-15 | DePuy Synthes Products, Inc. | Conditioned media and methods of making a conditioned media |
EP2379087B1 (en) | 2008-12-19 | 2014-08-20 | DePuy Synthes Products, LLC | Umbilical cord tissue derived cells for treating neuropathic pain and spasticity |
US10557116B2 (en) | 2008-12-19 | 2020-02-11 | DePuy Synthes Products, Inc. | Treatment of lung and pulmonary diseases and disorders |
EP2379089B1 (en) | 2008-12-19 | 2019-04-17 | DePuy Synthes Products, Inc. | Regeneration and repair of neural tissue following injury |
AU2010229651B2 (en) | 2009-03-26 | 2014-05-08 | Advanced Technologies And Regenerative Medicine, Llc | Human umbilical cord tissue cells as therapy for Alzheimer' s disease |
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-
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