JP2013515480A - ヒト胚性幹細胞の分化 - Google Patents
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Abstract
Description
本発明は、多能性幹細胞からのインスリン産生細胞への分化を促進させるための方法を提供する。詳細には、本発明は、NKX6.1及びインスリン、並びに最小量のグルカゴンを共発現する、膵臓内分泌系に特徴的なマーカーを発現する細胞を産生する方法を提供する。
a.多能性幹細胞を培養する工程、
b.多能性幹細胞を、胚体内胚葉系(definitive endoderm lineage)に特徴的なマーカーを発現する細胞へと分化させる工程、
c.胚体内胚葉系に特徴的なマーカーを発現する細胞を、膵臓内胚葉系に特徴的なマーカーを発現する細胞へと分化させる工程、
d.膵臓内胚葉系に特徴的なマーカーを発現する細胞を、プロテインキナーゼC活性化因子を追加した培地で処理することにより、膵臓内胚葉系に特徴的なマーカーを発現する細胞を、NKX6.1及びインスリン、並びに最小量のグルカゴンを共発現する、膵臓内分泌系に特徴的なマーカーを発現する細胞へと分化させる工程。
幹細胞は、単一の細胞レベルにおいて自己再生及び分化して、自己再生前駆細胞、非再生前駆細胞、及び最終分化細胞を含む、後代細胞を産生する、能力で定義される未分化細胞である。幹細胞は、複数の胚葉(内胚葉、中胚葉、及び外胚葉)から様々な細胞系の機能的細胞へとin vitroで分化する能力、並びに移植後に複数の胚葉の組織を生じ、及び胚盤胞への注入後、全部ではないとしても大部分の組織に実質的に寄与する能力によっても特徴付けられる。
多能性幹細胞の特徴付け
多能性幹細胞は、ステージ特異的胚抗原(SSEA)3及び4、並びにTra−1−60及びTra−1−81と呼ばれる抗体を使用して検出可能なマーカーのうちの1つ以上を発現する(Thomsonら,Science 282:1145,1998)。多能性幹細胞をin vitroで分化させると、SSEA−4、Tra−1−60、及びTra−1−81(存在する場合)の発現が減少し、SSEA−1の発現が上昇する。未分化の多能性幹細胞は通常アルカリホスファターゼ活性を有し、細胞を4%パラホルムアルデヒドで固定した後、製造業者(Vector Laboratories,Burlingame Calif.)の説明書に従ってVector Redを基質として発生させることによって検出可能である。未分化の多能性幹細胞は、OCT4及びTERTも通常発現し、RT−PCRにより検出される。
使用が可能な多能性幹細胞の種類としては、妊娠期間中の任意の時期(必ずしもではないが、通常は妊娠約10〜12週よりも前)に採取した前胚性組織(例えば、胚盤胞など)、胚性組織又は胎児組織などの、妊娠後に形成される組織に由来する多能性細胞の樹立株が含まれる。非限定的な例は、例えばヒト胚性幹細胞株H1、H7、及びH9(WiCell)などのヒト胚性幹細胞又はヒト胚生殖細胞の確立株である。それらの細胞の最初の樹立又は安定化中に本開示の組成物を使用することも想定され、その場合、供給源となる細胞は、供給源となる組織から直接採取した一次多能性細胞であろう。フィーダー細胞の不在下で既に培養された多能性幹細胞集団から採取した細胞も好適である。例えば、BG01v(BresaGen(Athens,GA))などの変異ヒト胚性幹細胞株も好適である。
一実施形態では、多能性幹細胞は、典型的にはフィーダー細胞の層上で培養され、このフィーダー細胞は、多能性幹細胞を様々な方法で支持する。あるいは、多能性幹細胞を、フィーダー細胞を本質的に含まないにも関わらず、細胞を実質的に分化させることなく多能性幹細胞の増殖を支持するような培養システム中で培養する。フィーダー細胞不含培養における多能性幹細胞の、分化を伴わない増殖は、あらかじめ別の細胞型を培養することにより馴化培地を使用して支持される。あるいは、フィーダー細胞不含培養における多能性幹細胞の、分化を伴わない増殖は、既知組成培地を使用して支持される。
一実施形態では、本発明は、多能性幹細胞から、膵臓内胚葉系に特徴的なマーカーを発現する細胞を産生するための方法を提供し、この方法は以下の工程a、b、c及びdを包含する:
a.多能性幹細胞を培養する工程、
b.多能性幹細胞を、胚体内胚葉系に特徴的なマーカーを発現する細胞へと分化させる工程、
c.胚体内胚葉系に特徴的なマーカーを発現する細胞を、膵臓内胚葉系に特徴的なマーカーを発現する細胞へと分化させる工程、
d.膵臓内胚葉系に特徴的なマーカーを発現する細胞を、膵内分泌系に特徴的なマーカーを発現する細胞へと分化させる工程。
胚体内胚葉系に特徴的なマーカーを発現する細胞の形成は、以下の特定のプロトコルの前後に、マーカーの存在に関して試験することにより決定され得る。多能性幹細胞は、典型的にはそのようなマーカーを最小量発現する。したがって、多能性細胞の分化は、細胞がそれらの発現を開始した際に検出される。
胚体内胚葉系に特徴的なマーカーを発現する細胞は、当該技術分野の任意の方法、又は本発明で提案する任意の方法により、膵臓内胚葉系に特徴的なマーカーを発現する細胞へと分化され得る。
一実施形態では、膵臓内胚葉系に特徴的なマーカーを発現する細胞は、膵臓内分泌系に特徴的なマーカーを発現する細胞に更に分化する。
一態様では、本発明は、I型糖尿病に罹患しているか、あるいはI型糖尿病を発症するリスクを有する患者を治療する方法を提供する。一実施形態では、この方法は、多能性幹細胞を培養する工程と、多能性幹細胞を、膵臓内分泌系に特徴的なマーカーを発現する細胞へとin vitroで分化させる工程と、膵臓内分泌系に特徴的なマーカーを発現する細胞を患者に移植する工程と、を含む。
インスリン及びNKX6.1、並びに最小量のグルカゴンを共発現する、膵臓内分泌系に特徴的なマーカーを発現する細胞集団の形成
ヒト胚性幹細胞株H1細胞を、MATRIGEL(登録商標)(1:30希釈)(BD Biosciences;カタログ# 356231)をコーティングしたディッシュと0.2%のFBS、100ng/mLのアクチビンA(PeproTech;カタログ#120−14)、及び20ng/mLのWNT−3a(R&D Systems;カタログ# 1324−WN/CF)を添加したRPMI培地(Invitrogen;カタログ#:22400)により1日培養した後で、0.5%のFBS及び100ng/mLのアクチビンAを添加したRPMI培地で更に2日間にわたって処理し(ステージ1)、次いで、
a.2%のFBS及び50ng/mLのFGF7(PeproTech;カタログ#100−19)を添加したDMEM/F12(Invitrogen;カタログ# 11330−032)で3日間にわたって処理し(ステージ2)、次いで、
b.1%のB27、50ng/mLのFGF7、0.25μMのシクロパミン−KAAD(Calbiochem;カタログ# 239804)、及び100ng/mLのノギン(R&D Systems;カタログ# 3344−NG)を添加したDMEM(高グルコース)(Invitrogen;カタログ# 10569)で4日間にわたって培養し(ステージ3)、次いで
c.1%のB27(Invitrogen;カタログ# 0791)、100ng/mLのノギン、1μMのALK5阻害剤II(Axxora;カタログ# ALX−270−445)、及び500nMのTBP((2S,5S)−(E,E)−8−(5−(4−(トリフルオロメチル)フェニル)−2,4−ペンタジエノイルアミノ(pentadiemoylamino))ベンゾラクタム)(Calbiochem;カタログ# 565740)を添加したDMEM(高グルコース)で6日間にわたって培養する(ステージ4)。
a.2%のFBS及び50ng/mLのFGF7を添加したDMEM/F12で3日間にわたって処理し(ステージ2)、次いで
b.1%のB27、0.25μMのシクロパミン−KAAD、2μMのレチノイン酸(RA)、及び100ng/mLのノギンを添加したDMEM(高グルコース)で4日間にわたって処理し(ステージ3)、次いで
c.処理1:1%のB27、100ng/mLのノギン、1μMのALK5阻害剤II、及び500nMのTBPを添加したDMEM(高グルコース)で6日間(ステージ4、処理1)、又は
d.処理2:1%のB27、100ng/mLのノギン、1μMのALK5阻害剤II、及び100nMのTBPを添加したDMEM(高グルコース)で6日間(ステージ4、処理2)、又は
e.処理3:1%のB27、100ng/mLのノギン、1μMのALK5阻害剤II、及び20nMのTBPを添加したDMEM(高グルコース)で6日間(ステージ4、処理3)、又は
f.処理4:1%のB27、100ng/mLのノギン、及び1μMのALK5阻害剤IIを添加したDMEM(高グルコース)で6日間(ステージ4、処理4)にわたって処理した。
a.2%のFBS及び50ng/mLのFGF7を添加したDMEM/F12で3日間にわたって処理し(ステージ2)、次いで
b.1%のB27、0.25μMのシクロパミン−KAAD、2μMのレチノイン酸(RA)、及び100ng/mLのノギンを添加したDMEM(高グルコース)で4日間にわたって処理し(ステージ3)、次いで
c.処理5:1%のB27、100ng/mLのノギン、1μMのALK5阻害剤II、及び500nMのTBPを添加したDMEM(高グルコース)で6日間(ステージ4、処理5)、又は
d.処理6:1%のB27、100ng/mLのノギン、1μMのALK5阻害剤II、500nMのTPB、及び5μMのGO 6976を添加したDMEM(高グルコース)で6日間(ステージ4、処理6)、又は
e.処理7:1%のB27、100ng/mLのノギン、及び1μMのALK5阻害剤IIを添加したDMEM(高グルコース)で処理し(ステージ4、処理7)、次いで
f.1%のB27を添加したDMEM(高グルコース)で4日間にわたって処理した(ステージ5)。
インスリン及びNKX6.1、並びに最小量のグルカゴンを共発現する、膵臓内分泌系に特徴的なマーカーを発現する細胞集団を形成する別法
異なる実験において、ヒト胚性幹細胞株H1細胞を、MATRIGEL(登録商標)(1:30希釈)をコーティングしたディッシュと、0.2%のFBS、100ng/mLのアクチビンA、及び20ng/mL WNT−3aを添加したRPMI培地により1日培養し、次いで0.5%のFBS及び100ng/mLのアクチビンAを添加したRPMI培地で更に2日間にわたって処理し(ステージ1)、次いで
a.2%のFBS及び50ng/mLのFGF7を添加したDMEM/F12で3日間にわたって処理し(ステージ2)、次いで
b.処理8:1%のB27、50ng/mLのFGF7、0.25μMのシクロパミン−KAAD、2μMのレチノイン酸(RA)、100ng/mLのノギン、20ng/mLのアクチビンA、及びp38キナーゼ阻害剤(米国特許第6,214,830号に開示されるもの、2.5μM)を添加したDMEM(高グルコース)で4日間(ステージ3、処理8)、又は
c.処理9:1%のB27、0.25μMのシクロパミン−KAAD、2μMのレチノイン酸(RA)、及び100ng/mLのノギンを添加したDMEM(高グルコース)で4日間(ステージ3、処理9)、次いで
d.1%のB27、100ng/mLのノギン、1μMのALK5阻害剤II、及び500nMのTPBを添加したDMEM(高グルコース)で6日間にわたって処理した(ステージ4)。
インスリン及びNKX6.1、並びに最小量のグルカゴンを共発現する、膵臓内分泌系に特徴的なマーカーを発現する細胞集団を形成する別法
別の実験において、ヒト胚性幹細胞株H1細胞を、MATRIGEL(登録商標)(1:30希釈)をコーティングしたディッシュと、0.2%のFBS、100ng/mLのアクチビンA、及び20ng/mLのWNT−3aを添加したRPMI培地により1日培養し、次いで0.5%のFBS及び100ng/mLのアクチビンAを添加したRPMI培地で更に2日間にわたって処理し(ステージ1)、次いで
a.2%のFBS及び50ng/mLのFGF7を添加したDMEM/F12で3日間にわたって処理し(ステージ2)、次いで
b.1%のB27、50ng/mLのFGF7、0.25μMのシクロパミン−KAAD、2μMのレチノイン酸(RA)、100ng/mLのノギン、20ng/mLのアクチビンA、及びp38キナーゼ阻害剤(JNJ3026582、2.5μM)を添加したDMEM(高グルコース)で4日間にわたって処理し(ステージ3)、次いで
c.処理10:1%のB27、100ng/mLのノギン、1μMのALK5阻害剤II、及び500nMのTPBを添加したDMEM(高グルコース)で6日間(ステージ4、処理10)、又は
d.処理11:1%のB27、100ng/mLのノギン、1μMのALK5阻害剤II、及び500nMのTPBを添加したDMEM(高グルコース)で9日間(ステージ4、処理11)、又は
e.処理12:1%のB27、100ng/mLのノギン、1μMのALK5阻害剤II、及び500nMのTPBを添加したDMEM(高グルコース)で12日間にわたって処理した(ステージ4、処理12)。
重症複合免疫不全(SCID)−beige(Bg)マウスへの、本発明の細胞の移植
ヒト胚性幹細胞株H1細胞を、MATRIGEL(登録商標)(1:30希釈)をコーティングしたディッシュと、0.2%のFBS、100ng/mLのアクチビンA、及び20ng/mLのWNT−3aを添加したRPMI培地により1日培養し、次いで0.5%のFBS及び100ng/mLのアクチビンAを添加したRPMI培地で更に2日間にわたって処理し(ステージ1)、次いで
a.2%のFBS及び50ng/mLのFGF7を添加したDMEM/F12で3日間にわたって処理し(ステージ2)、次いで
b.1%のB27、50ng/mLのFGF7、0.25μMのシクロパミン−KAAD、及び100ng/mLのノギンを添加したDMEM(高グルコース)で4日間にわたって処理し(ステージ3)、次いで
c.1%のB27、100ng/mLのノギン、1μMのALK5阻害剤II、及び500nMのTBPを添加したDMEM(高グルコース)で6日間にわたって処理した(ステージ4)。
PDX1及びNKX6.1を共発現する、膵臓内胚葉系に特徴的なマーカーを発現する細胞集団を形成する別法
簡潔に述べると、ヒト胚性幹細胞株H1細胞を、MATRIGEL(登録商標)(1:30希釈)をコーティングしたディッシュと、0.2%のFBS、100ng/mLのアクチビンA、及び20ng/mLのWNT−3aを追加したRPMI培地により1日培養した後で、0.5%のFBS及び100ng/mLのアクチビンAを追加したRPMI培地で更に2日間にわたって処理し(ステージ1)、次いで
a.2%のFBS及び50ng/mLのFGF7を添加したDMEM/F12で3日間にわたって処理し(ステージ2)、次いで
b.1%のB27、0.25μMのシクロパミン−KAAD、2μMのレチノイン酸(RA)、及び100ng/mLのノギンを添加したDMEM(高グルコース)で4日間にわたって処理し(ステージ3)、次いで
c.1%のB27、100ng/mLのノギン、1μMのALK5阻害剤II、20nM PMA、又は100nMのTPB、又は20nMのホルボール−12,13−ジブチラート(PDBu)(Calbioche、カタログ#524390)を添加したDMEM(高グルコース)で6日間にわたって処理した(ステージ4)。
膵臓内胚葉系に特徴的なマーカーを発現する細胞の、プロテインキナーゼC活性化因子による処理
簡潔に述べると、ヒト胚性幹細胞株H1細胞を、MATRIGEL(登録商標)(1:30希釈)をコーティングしたディッシュと、0.2%のFBS、100ng/mLのアクチビンA、及び20ng/mLのWNT−3aを追加したRPMI培地により1日培養した後で、0.5%のFBS、及び100ng/mLのアクチビンAを追加したRPMI培地で更に2日間にわたって処理し(ステージ1)、次いで
a.2%のFBS及び50ng/mLのFGF7を添加したDMEM/F12で3日間にわたって処理し(ステージ2)、次いで
b.T1:1%のB27、0.25μMのシクロパミン−KAAD、2μMのレチノイン酸(RA)、100ng/mLのノギン、及び50ng/mLのFGF10を添加したDMEM(高グルコース)で4日間(ステージ3、T1)、又は
T2:1%のB27、0.25μMのシクロパミン−KAAD、2μMのレチノイン酸(RA)、100ng/mLのノギン、50ng/mLのFGF10、及び100nMのTPBを添加したDMEM(高グルコース)で4日間にわたって処理し(ステージ3、T2)、次いで
c.1%のB27、100ng/mLのノギン、及び1μMのALK5阻害剤IIを添加したDMEM(高グルコース)で6日間にわたって処理した(ステージ4)。
Claims (7)
- NKX6.1及びインスリンを共発現する、膵臓内分泌系に特徴的なマーカーを発現する細胞集団であって、前記集団の10%未満の細胞がグルカゴンを発現する、細胞集団。
- 前記細胞の少なくとも30%がNKX6.1を発現する、請求項1に記載の細胞集団。
- 前記細胞の少なくとも40%がNKX.6.1を発現する、請求項1に記載の細胞集団。
- 前記細胞の少なくとも50%がNKX6.1を発現する、請求項1に記載の細胞集団。
- 前記細胞の少なくとも60%がNKX6.1を発現する、請求項1に記載の細胞集団。
- 前記細胞の少なくとも5%がインスリンを発現する、請求項1に記載の細胞集団。
- NKX6.1及びインスリンを共発現する、膵臓内分泌系に特徴的なマーカーを発現する細胞集団を生成する方法であって、前記集団の10%未満の細胞がグルカゴンを発現し、前記方法が、
a.多能性幹細胞を培養する工程と、
b.前記多能性幹細胞を、胚体内胚葉系(definitive endoderm lineage)に特徴的なマーカーを発現する細胞へと分化させる工程と、
c.前記胚体内胚葉系に特徴的なマーカーを発現する細胞を、膵臓内胚葉系に特徴的なマーカーを発現する細胞へと分化させる工程と、
d.前記膵臓内胚葉系に特徴的なマーカーを発現する細胞を、BMP阻害能を有する因子、TGFβ受容体シグナル伝達阻害剤、及びプロテインキナーゼC活性化因子を追加した培地で培養することにより、前記膵臓内胚葉系に特徴的なマーカーを発現する細胞を、NKX6.1及びインスリン、並びに最小量のグルカゴンを共発現する、前記膵臓内分泌系に特徴的なマーカーを発現する細胞へと分化させる工程と、を含む、方法。
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Families Citing this family (52)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US9080145B2 (en) | 2007-07-01 | 2015-07-14 | Lifescan Corporation | Single pluripotent stem cell culture |
RU2473685C2 (ru) | 2007-07-31 | 2013-01-27 | Лайфскен, Инк. | Дифференцировка человеческих эмбриональных стволовых клеток |
WO2009070592A2 (en) | 2007-11-27 | 2009-06-04 | Lifescan, Inc. | Differentiation of human embryonic stem cells |
BR122017025207B1 (pt) | 2008-02-21 | 2021-03-16 | Centocor Ortho Biotech Inc | superfície que faz parte de um recipiente ou matriz destinada para uso em uma cultura de células ou análises, desprovida de uma camada de células alimentadoras e desprovida de uma camada adsorvente |
CA2729121C (en) | 2008-06-30 | 2019-04-09 | Centocor Ortho Biotech Inc. | Differentiation of pluripotent stem cells |
US9012218B2 (en) | 2008-10-31 | 2015-04-21 | Janssen Biotech, Inc. | Differentiation of human embryonic stem cells |
RU2522001C2 (ru) | 2008-10-31 | 2014-07-10 | Сентокор Орто Байотек Инк. | Дифференцирование человеческих эмбриональных стволовых клеток в линию панкреатических эндокринных клеток |
US8278106B2 (en) | 2008-11-14 | 2012-10-02 | Viacyte, Inc. | Encapsulation of pancreatic cells derived from human pluripotent stem cells |
CN107267442A (zh) | 2008-11-20 | 2017-10-20 | 詹森生物科技公司 | 微载体上的多能干细胞培养 |
KR101687344B1 (ko) | 2008-11-20 | 2016-12-16 | 얀센 바이오테크 인코포레이티드 | 평면 기재상의 세포 부착 및 배양을 위한 방법 및 조성물 |
KR20170118969A (ko) | 2009-07-20 | 2017-10-25 | 얀센 바이오테크 인코포레이티드 | 인간 배아 줄기 세포의 분화 |
BR112012017761A2 (pt) | 2009-12-23 | 2015-09-15 | Centocor Ortho Biotech Inc | diferenciação das células-tronco embrionárias humanas |
CN102791851B (zh) | 2010-03-01 | 2017-07-14 | 詹森生物科技公司 | 纯化衍生自多能干细胞的细胞的方法 |
AU2015268659B2 (en) * | 2010-05-12 | 2017-12-21 | Janssen Biotech, Inc. | Differentiation of human embryonic stem cells |
JP6050225B2 (ja) | 2010-05-12 | 2016-12-21 | 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 |
ES2660897T3 (es) | 2010-08-31 | 2018-03-26 | Janssen Biotech, Inc. | Diferenciación de células madre embrionarias humanas |
EP2611910B1 (en) | 2010-08-31 | 2018-01-17 | Janssen Biotech, Inc. | Differentiation of human embryonic stem cells |
JP6163104B2 (ja) | 2010-11-15 | 2017-07-12 | アクセラレイテッド・バイオサイエンシズ・コーポレーション | ヒト・トロホブラスト幹細胞からの神経幹細胞の生成 |
CN108220224A (zh) | 2011-06-21 | 2018-06-29 | 诺沃—诺迪斯克有限公司 | 自多潜能干细胞有效诱导定形内胚层 |
WO2013016194A1 (en) * | 2011-07-22 | 2013-01-31 | Yale University | Endometrial derived stem cells and their methods of use |
SG11201403473QA (en) | 2011-12-22 | 2014-10-30 | Janssen Biotech Inc | Differentiation of human embryonic stem cells into single hormonal insulin positive cells |
US9434920B2 (en) | 2012-03-07 | 2016-09-06 | Janssen Biotech, Inc. | Defined media for expansion and maintenance of pluripotent stem cells |
PT2844739T (pt) * | 2012-04-30 | 2019-10-01 | Univ Health Network | Métodos e composições para gerar progenitores pancreáticos e células beta funcionais a partir de hpscs |
KR102114209B1 (ko) | 2012-06-08 | 2020-05-25 | 얀센 바이오테크 인코포레이티드 | 인간 배아 줄기 세포의 췌장 내분비 세포로의 분화 |
JP6470687B2 (ja) * | 2012-09-03 | 2019-02-13 | ノヴォ ノルディスク アー/エス | 小分子を用いた多能性幹細胞からの膵臓内胚葉の作製 |
CA2891542C (en) | 2012-11-30 | 2021-12-14 | Accelerated Biosciences Corp. | Pancreatic progenitor cells expressing betatrophin and insulin |
US10370644B2 (en) | 2012-12-31 | 2019-08-06 | Janssen Biotech, Inc. | Method for making human pluripotent suspension cultures and cells derived therefrom |
US10344264B2 (en) * | 2012-12-31 | 2019-07-09 | Janssen Biotech, Inc. | Culturing of human embryonic stem cells at the air-liquid interface for differentiation into pancreatic endocrine cells |
CA2896750A1 (en) | 2012-12-31 | 2014-07-03 | Janssen Biotech, Inc. | Suspension and clustering of human pluripotent cells for differentiation into pancreatic endocrine cells |
CN111394298A (zh) * | 2012-12-31 | 2020-07-10 | 詹森生物科技公司 | 使用hb9调节子使人胚胎干细胞分化为胰腺内分泌细胞的方法 |
US8859286B2 (en) | 2013-03-14 | 2014-10-14 | Viacyte, Inc. | In vitro differentiation of pluripotent stem cells to pancreatic endoderm cells (PEC) and endocrine cells |
US20170029778A1 (en) | 2013-06-11 | 2017-02-02 | President And Fellows Of Harvard College | Sc-beta cells and compositions and methods for generating the same |
SG11201609473XA (en) | 2014-05-16 | 2016-12-29 | Janssen Biotech Inc | Use of small molecules to enhance mafa expression in pancreatic endocrine cells |
US10443042B2 (en) | 2014-12-18 | 2019-10-15 | President And Fellows Of Harvard College | Serum-free in vitro directed differentiation protocol for generating stem cell-derived beta cells and uses thereof |
WO2016100930A1 (en) | 2014-12-18 | 2016-06-23 | President And Fellows Of Harvard College | Methods for generating stem cell-derived b cells and methods of use thereof |
WO2016100909A1 (en) | 2014-12-18 | 2016-06-23 | President And Fellows Of Harvard College | METHODS FOR GENERATING STEM CELL-DERIVED β CELLS AND USES THEREOF |
CN108699515A (zh) | 2016-02-24 | 2018-10-23 | 诺和诺德股份有限公司 | 由人多能干细胞衍生的内分泌祖细胞生成功能性β细胞 |
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 |
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 |
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 |
US10391156B2 (en) | 2017-07-12 | 2019-08-27 | Viacyte, Inc. | University donor cells and related methods |
BR112020009275A2 (pt) | 2017-11-15 | 2020-10-27 | Semma Therapeutics, Inc. | composições de fabricação de célula de ilhota e métodos de uso |
AU2019320072A1 (en) | 2018-08-10 | 2021-02-25 | Vertex Pharmaceuticals Incorporated | Stem cell derived islet differentiation |
US20200080107A1 (en) | 2018-09-07 | 2020-03-12 | Crispr Therapeutics Ag | Universal donor cells |
AU2020283056B2 (en) | 2019-05-31 | 2023-06-08 | Viacyte, Inc. | A biocompatible membrane composite |
WO2020243668A1 (en) | 2019-05-31 | 2020-12-03 | W. L. Gore & Associates, Inc. | Cell encapsulation devices with controlled oxygen diffusion distances |
CN114206407A (zh) | 2019-05-31 | 2022-03-18 | W.L.戈尔及同仁股份有限公司 | 生物相容性膜复合材料 |
AU2020282355B2 (en) | 2019-05-31 | 2023-11-02 | Viacyte, Inc. | A biocompatible membrane composite |
JP2022547053A (ja) | 2019-09-05 | 2022-11-10 | クリスパー セラピューティクス アクチェンゲゼルシャフト | ユニバーサルドナー細胞 |
CA3150235A1 (en) | 2019-09-05 | 2021-03-11 | Alireza Rezania | UNIVERSAL DONOR CELLS |
RU2743710C1 (ru) * | 2019-12-11 | 2021-02-24 | федеральное государственное бюджетное образовательное учреждение высшего образования "Новосибирский государственный медицинский университет" Министерства здравоохранения Российской Федерации (ФГБОУ ВО НГМУ Минздрава России) | Средство, снижающее относительное содержание низкодифференцированных и повышающее относительное содержание высокодифференцированных клеток в инвазивной карциноме молочной железы неспецифического типа |
WO2022144856A1 (en) | 2020-12-31 | 2022-07-07 | Crispr Therapeutics Ag | Universal donor cells |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2009132083A2 (en) * | 2008-04-22 | 2009-10-29 | President And Fellows Of Harvard College | Compositions and methods for promoting the generation of pdx1+ pancreatic cells |
JP2011504753A (ja) * | 2007-11-27 | 2011-02-17 | ライフスキャン・インコーポレイテッド | ヒト胚性幹細胞の分化 |
Family Cites Families (258)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3209652A (en) | 1961-03-30 | 1965-10-05 | Burgsmueller Karl | Thread whirling method |
AT326803B (de) | 1968-08-26 | 1975-12-29 | Binder Fa G | Maschenware sowie verfahren zur herstellung derselben |
US3935067A (en) * | 1974-11-22 | 1976-01-27 | Wyo-Ben Products, Inc. | Inorganic support for culture media |
CA1201400A (en) | 1982-04-16 | 1986-03-04 | Joel L. Williams | Chemically specific surfaces for influencing cell activity during culture |
US4499802A (en) | 1982-09-29 | 1985-02-19 | Container Graphics Corporation | Rotary cutting die with scrap ejection |
US4537773A (en) | 1983-12-05 | 1985-08-27 | E. I. Du Pont De Nemours And Company | α-Aminoboronic acid derivatives |
US4557264A (en) | 1984-04-09 | 1985-12-10 | Ethicon Inc. | Surgical filament from polypropylene blended with polyethylene |
US4734578A (en) * | 1985-03-27 | 1988-03-29 | Olympus Optical Co., Ltd. | Two-dimensional scanning photo-electric microscope |
US5215893A (en) * | 1985-10-03 | 1993-06-01 | Genentech, Inc. | Nucleic acid encoding the ba chain prodomains of inhibin and method for synthesizing polypeptides using such nucleic acid |
US5089396A (en) * | 1985-10-03 | 1992-02-18 | Genentech, Inc. | Nucleic acid encoding β chain prodomains of inhibin and method for synthesizing polypeptides using such nucleic acid |
US4737578A (en) | 1986-02-10 | 1988-04-12 | The Salk Institute For Biological Studies | Human inhibin |
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 |
US5567612A (en) * | 1986-11-20 | 1996-10-22 | Massachusetts Institute Of Technology | Genitourinary cell-matrix structure for implantation into a human and a method of making |
US5759830A (en) * | 1986-11-20 | 1998-06-02 | Massachusetts Institute Of Technology | Three-dimensional fibrous scaffold containing attached cells for producing vascularized tissue in vivo |
CA1340581C (en) * | 1986-11-20 | 1999-06-08 | Joseph P. Vacanti | Chimeric neomorphogenesis of organs by controlled cellular implantation using artificial matrices |
NZ229354A (en) | 1988-07-01 | 1990-09-26 | Becton Dickinson Co | Treating polymer surfaces with a gas plasma and then applying a layer of endothelial cells to the surface |
EP0363125A3 (en) | 1988-10-03 | 1990-08-16 | Hana Biologics Inc. | Proliferated pancreatic endocrine cell product and process |
SU1767433A1 (ru) | 1989-11-27 | 1992-10-07 | Пермский государственный медицинский институт | Способ определени инсулинорезистентности имунного генеза у больных сахарным диабетом I типа |
US5837539A (en) * | 1990-11-16 | 1998-11-17 | Osiris Therapeutics, Inc. | Monoclonal antibodies for human mesenchymal stem cells |
JP3370324B2 (ja) | 1991-04-25 | 2003-01-27 | 中外製薬株式会社 | ヒトインターロイキン−6受容体に対する再構成ヒト抗体 |
US5449383A (en) * | 1992-03-18 | 1995-09-12 | Chatelier; Ronald C. | Cell growth substrates |
GB9206861D0 (en) | 1992-03-28 | 1992-05-13 | Univ Manchester | Wound healing and treatment of fibrotic disorders |
CA2114282A1 (en) | 1993-01-28 | 1994-07-29 | Lothar Schilder | Multi-layered implant |
JP3525221B2 (ja) | 1993-02-17 | 2004-05-10 | 味の素株式会社 | 免疫抑制剤 |
AU687386B2 (en) | 1993-04-08 | 1998-02-26 | Human Cell Cultures, Inc. | Cell culturing method and medium |
US5523226A (en) * | 1993-05-14 | 1996-06-04 | Biotechnology Research And Development Corp. | Transgenic swine compositions and methods |
GB9310557D0 (en) * | 1993-05-21 | 1993-07-07 | Smithkline Beecham Plc | Novel process and apparatus |
TW257671B (ja) | 1993-11-19 | 1995-09-21 | Ciba Geigy | |
US6001647A (en) | 1994-04-28 | 1999-12-14 | Ixion Biotechnology, Inc. | In vitro growth of functional islets of Langerhans and in vivo uses thereof |
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 |
US5834308A (en) * | 1994-04-28 | 1998-11-10 | University Of Florida Research Foundation, Inc. | In vitro growth of functional islets of Langerhans |
US6083903A (en) | 1994-10-28 | 2000-07-04 | Leukosite, Inc. | Boronic ester and acid compounds, synthesis and uses |
CN1075387C (zh) | 1994-12-29 | 2001-11-28 | 中外制药株式会社 | 含有il-6拮抗剂的抗肿瘤剂的作用增强剂 |
US5843780A (en) * | 1995-01-20 | 1998-12-01 | Wisconsin Alumni Research Foundation | Primate embryonic stem cells |
US5718922A (en) * | 1995-05-31 | 1998-02-17 | Schepens Eye Research Institute, Inc. | Intravitreal microsphere drug delivery and method of preparation |
US5908782A (en) * | 1995-06-05 | 1999-06-01 | Osiris Therapeutics, Inc. | Chemically defined medium for human mesenchymal stem cells |
US5681561A (en) | 1995-06-07 | 1997-10-28 | Life Medical Sciences, Inc. | Compositions and methods for improving autologous fat grafting |
JP2001508302A (ja) | 1997-01-10 | 2001-06-26 | ライフ テクノロジーズ,インコーポレイテッド | 胚性幹細胞血清置換 |
UA65572C2 (en) | 1997-04-24 | 2004-04-15 | Ortho Mcneil Pharm Inc | Substituted imidazoles, intermediate compounds for the preparation thereof, a method for the preparation of substituted imidazoles and a method for the treatment of inflammatory diseases |
CA2294944A1 (en) * | 1997-07-03 | 1999-01-14 | Osiris Therapeutics, Inc. | Human mesenchymal stem cells from peripheral blood |
EP1538206B1 (en) * | 1997-09-16 | 2010-03-24 | Centocor, Inc. | Method for the complete chemical synthesis and assembly of genes and genomes |
US6670127B2 (en) | 1997-09-16 | 2003-12-30 | Egea Biosciences, Inc. | Method for assembly of a polynucleotide encoding a target polypeptide |
JP3880795B2 (ja) * | 1997-10-23 | 2007-02-14 | ジェロン・コーポレーション | フィーダー細胞を含まない培養物中で、霊長類由来始原幹細胞を増殖させるための方法 |
ZA9811898B (en) * | 1997-12-29 | 2000-06-28 | Ortho Mcneil Pharm Inc | Anti-Inflammatory Compounds. |
AU755888B2 (en) | 1998-03-18 | 2003-01-02 | Mesoblast International Sarl | Mesenchymal stem cells for prevention and treatment of immune responses in transplantation |
MY132496A (en) * | 1998-05-11 | 2007-10-31 | Vertex Pharma | Inhibitors of p38 |
US6413773B1 (en) | 1998-06-01 | 2002-07-02 | The Regents Of The University Of California | Phosphatidylinositol 3-kinase inhibitors as stimulators of endocrine differentiation |
US7410798B2 (en) * | 2001-01-10 | 2008-08-12 | Geron Corporation | Culture system for rapid expansion of human embryonic stem cells |
US6667176B1 (en) * | 2000-01-11 | 2003-12-23 | Geron Corporation | cDNA libraries reflecting gene expression during growth and differentiation of human pluripotent stem cells |
US6610540B1 (en) | 1998-11-18 | 2003-08-26 | California Institute Of Technology | Low oxygen culturing of central nervous system progenitor cells |
US6413556B1 (en) * | 1999-01-08 | 2002-07-02 | Sky High, Llc | Aqueous anti-apoptotic compositions |
US6458593B1 (en) * | 1999-01-21 | 2002-10-01 | Vitro Diagnostics, Inc. | Immortalized cell lines and methods of making the same |
US6815203B1 (en) * | 1999-06-23 | 2004-11-09 | Joslin Diabetes Center, Inc. | Methods of making pancreatic islet cells |
US6333029B1 (en) * | 1999-06-30 | 2001-12-25 | Ethicon, Inc. | Porous tissue scaffoldings for the repair of regeneration of tissue |
US6306424B1 (en) * | 1999-06-30 | 2001-10-23 | Ethicon, Inc. | Foam composite for the repair or regeneration of tissue |
WO2001023528A1 (en) | 1999-09-27 | 2001-04-05 | University Of Florida Research Foundation | Reversal of insulin-dependent diabetes by islet-producing stem cells, islet progenitor cells and islet-like structures |
US6685936B2 (en) * | 1999-10-12 | 2004-02-03 | Osiris Therapeutics, Inc. | Suppressor cells induced by culture with mesenchymal stem cells for treatment of immune responses in transplantation |
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 |
WO2001042789A1 (en) | 1999-12-13 | 2001-06-14 | The Scripps Research Institute | MARKERS FOR IDENTIFICATION AND ISOLATION OF PANCREATIC ISLET α AND β CELL PROGENITORS |
US7005252B1 (en) * | 2000-03-09 | 2006-02-28 | Wisconsin Alumni Research Foundation | Serum free cultivation of primate embryonic stem cells |
US7439064B2 (en) | 2000-03-09 | 2008-10-21 | Wicell Research Institute, Inc. | Cultivation of human embryonic stem cells in the absence of feeder cells or without conditioned medium |
US6436704B1 (en) * | 2000-04-10 | 2002-08-20 | Raven Biotechnologies, Inc. | Human pancreatic epithelial progenitor cells and methods of isolation and use thereof |
US6458589B1 (en) | 2000-04-27 | 2002-10-01 | Geron Corporation | Hepatocyte lineage cells derived from pluripotent stem cells |
KR100947577B1 (ko) * | 2000-06-26 | 2010-03-15 | 엔씨 메디컬 리서치 가부시키가이샤 | 신경계 세포로 분화할 수 있는 세포를 포함하는 세포분획 |
ES2372028T3 (es) * | 2000-10-23 | 2012-01-13 | Glaxosmithkline Llc | Nuevo compuesto de 8h-pirido[2,3-d]pirimidin-7-ona trisustituida para el tratamiento de enfermedades mediadas por la csbp/p38 quinasa. |
YU46603A (sh) | 2000-12-08 | 2006-05-25 | Ortho-Mcneil Pharmaceutical Inc. | Indazolil-supstituisana jedinjenja pirolina, kao inhibitori kinaze |
RU2275373C2 (ru) | 2000-12-08 | 2006-04-27 | Орто-Макнейл Фармасьютикал, Инк. | Макрогетероциклические соединения |
US6599323B2 (en) * | 2000-12-21 | 2003-07-29 | Ethicon, Inc. | Reinforced tissue implants and methods of manufacture and use |
US20040121460A1 (en) | 2001-01-24 | 2004-06-24 | Lumelsky Nadya L | Differentiation of stem cells to pancreatic endocrine cells |
JP4162491B2 (ja) | 2001-01-25 | 2008-10-08 | アメリカ合衆国 | ボロン酸化合物製剤 |
US6656488B2 (en) | 2001-04-11 | 2003-12-02 | Ethicon Endo-Surgery, Inc. | Bioabsorbable bag containing bioabsorbable materials of different bioabsorption rates for tissue engineering |
DE10290025T1 (de) | 2001-04-19 | 2003-10-09 | Develogen Ag | Verfahren zur Differenzierung von Stammzellen in Insulin-produzierende Zellen |
ATE421991T1 (de) | 2001-04-24 | 2009-02-15 | Ajinomoto Kk | Stammzellen und verfahren zu deren trennung |
EP1393066A4 (en) | 2001-05-15 | 2006-01-25 | Rappaport Family Inst For Res | INSULIN-PRODUCING CELLS DERIVED FROM HUMAN EMBRYONAL STEM CELLS |
US6626950B2 (en) * | 2001-06-28 | 2003-09-30 | Ethicon, Inc. | Composite scaffold with post anchor for the repair and regeneration of tissue |
KR100418195B1 (ko) | 2001-07-05 | 2004-02-11 | 주식회사 우리기술 | 전력케이블의 다중절연진단장치 및 그 방법 |
GB0117583D0 (en) * | 2001-07-19 | 2001-09-12 | Astrazeneca Ab | Novel compounds |
CA2456981C (en) * | 2001-08-06 | 2012-02-28 | Bresagen, Inc. | Alternative compositions and methods for the culture of stem cells |
US6617152B2 (en) * | 2001-09-04 | 2003-09-09 | Corning Inc | Method for creating a cell growth surface on a polymeric substrate |
EP1298201A1 (en) | 2001-09-27 | 2003-04-02 | Cardion AG | Process for the production of cells exhibiting an islet-beta-cell-like state |
CA2463914A1 (en) * | 2001-10-18 | 2003-04-24 | Ixion Biotechnology, Inc. | Conversion of liver stem and progenitor cells to pancreatic functional cells |
AU2002359390A1 (en) * | 2001-11-09 | 2003-05-19 | Artecel Sciences, Inc. | Endocrine pancreas differentiation of adipose tissue-derived stromal cells and uses thereof |
JP4330995B2 (ja) | 2001-11-15 | 2009-09-16 | チルドレンズ メディカル センター コーポレーション | 絨毛膜絨毛、羊水、および胎盤からの胎児性幹細胞を単離、増殖、および分化させる方法、ならびにその治療的使用方法 |
KR101089591B1 (ko) | 2001-12-07 | 2011-12-05 | 제론 코포레이션 | 인간 배아 줄기세포 유래의 섬세포 |
WO2003053346A2 (en) | 2001-12-07 | 2003-07-03 | Macropore Biosurgery, Inc. | Systems and methods for treating patients with processed lipoaspirate cells |
AU2002218893A1 (en) | 2001-12-21 | 2003-07-09 | Thromb-X Nv | Compositions for the in vitro derivation and culture of embryonic stem (es) cell lines with germline transmission capability |
JP2005512593A (ja) | 2001-12-28 | 2005-05-12 | セルアーティス アーベー | 多能性のヒト胚盤胞由来幹細胞株の樹立方法 |
US20030162290A1 (en) | 2002-01-25 | 2003-08-28 | Kazutomo Inoue | Method for inducing differentiation of embryonic stem cells into functioning cells |
US20030180268A1 (en) | 2002-02-05 | 2003-09-25 | Anthony Atala | Tissue engineered construct for supplementing or replacing a damaged organ |
EP1498478A1 (en) * | 2002-04-17 | 2005-01-19 | Otsuka Pharmaceutical Co., Ltd. | Method of forming pancreatic beta cells from mesenchymal cells |
US20040161419A1 (en) * | 2002-04-19 | 2004-08-19 | Strom Stephen C. | Placental stem cells and uses thereof |
US7125878B2 (en) | 2002-05-08 | 2006-10-24 | Janssen Pharmaceutica | Substituted pyrroline kinase inhibitors |
US20060003446A1 (en) * | 2002-05-17 | 2006-01-05 | Gordon Keller | Mesoderm and definitive endoderm cell populations |
US20060122104A1 (en) | 2002-05-28 | 2006-06-08 | Presnell Sharon C | Methods for in vitro expansion and transdifferentiation of human pancreatic acinar cells into insulin-producing cells |
CN1671694A (zh) * | 2002-06-05 | 2005-09-21 | 詹森药业有限公司 | 作为激酶抑制剂的二吲哚基-顺丁烯二酰亚胺衍生物 |
GB0212976D0 (en) | 2002-06-06 | 2002-07-17 | Tonejet Corp Pty Ltd | Ejection method and apparatus |
CN1171991C (zh) | 2002-07-08 | 2004-10-20 | 徐如祥 | 人神经干细胞的培养方法 |
US6877147B2 (en) * | 2002-07-22 | 2005-04-05 | Broadcom Corporation | Technique to assess timing delay by use of layout quality analyzer comparison |
US7838290B2 (en) * | 2002-07-25 | 2010-11-23 | The Scripps Research Institute | Hematopoietic stem cells and methods of treatment of neovascular eye diseases therewith |
WO2004011621A2 (en) | 2002-07-29 | 2004-02-05 | Es Cell International Pte Ltd. | Multi-step method for the differentiation of insulin positive, glucose |
AU2003262628A1 (en) | 2002-08-14 | 2004-03-03 | University Of Florida | Bone marrow cell differentiation |
JP2005537803A (ja) | 2002-09-06 | 2005-12-15 | アムサイト インコーポレーティッド | Cd56陽性ヒト成体膵臓内分泌前駆細胞 |
US9969977B2 (en) * | 2002-09-20 | 2018-05-15 | Garnet Biotherapeutics | Cell populations which co-express CD49c and CD90 |
US20040062753A1 (en) * | 2002-09-27 | 2004-04-01 | Alireza Rezania | Composite scaffolds seeded with mammalian cells |
US20060252150A1 (en) | 2002-11-08 | 2006-11-09 | Linzhao Cheng | Human embryonic stem cell cultures, and compositions and methods for growing same |
US7144999B2 (en) * | 2002-11-23 | 2006-12-05 | Isis Pharmaceuticals, Inc. | Modulation of hypoxia-inducible factor 1 alpha expression |
US20060040385A1 (en) | 2002-12-05 | 2006-02-23 | Technion Research & Development Foundation Ltd. | Cultured human pancreatic islets, and uses thereof |
HUE028026T2 (en) | 2002-12-16 | 2016-11-28 | Technion Res & Dev Foundation | Breeding system free of native cells, free of foreign matter for human embryonic stem cells |
US20050118148A1 (en) | 2002-12-20 | 2005-06-02 | Roland Stein | Compositions and methods related to mammalian Maf-A |
WO2004067001A1 (ja) | 2003-01-29 | 2004-08-12 | Takeda Pharmaceutical Company Limited | 被覆製剤の製造法 |
RU2359671C2 (ru) | 2003-01-29 | 2009-06-27 | Такеда Фармасьютикал Компани Лимитед | Способ получения препарата с покрытием |
US20070155661A1 (en) | 2003-02-14 | 2007-07-05 | The Board Of Trustees Of The Leland Standord Junior University | Methods and compositions for modulating the development of stem cells |
WO2005045001A2 (en) * | 2003-02-14 | 2005-05-19 | The Board Of Trustees Of The Leland Stanford Junior University | Insulin-producing cells derived from stem cells |
WO2004087885A2 (en) | 2003-03-27 | 2004-10-14 | Ixion Biotechnology, Inc. | Method for transdifferentiation of non-pancreatic stem cells to the pancreatic pathway |
US20060194315A1 (en) * | 2003-03-31 | 2006-08-31 | Condie Brian G | Compositions and methods for the control, differentiaton and/or manipulation of pluripotent cells through a gamma-secretase signaling pathway |
US20090203141A1 (en) * | 2003-05-15 | 2009-08-13 | Shi-Lung Lin | Generation of tumor-free embryonic stem-like pluripotent cells using inducible recombinant RNA agents |
ES2597837T3 (es) | 2003-06-27 | 2017-01-23 | DePuy Synthes Products, Inc. | Células posparto derivadas de tejido de la placenta, y métodos de fabricación y utilización de los mismos |
IL161903A0 (en) * | 2003-07-17 | 2005-11-20 | Gamida Cell Ltd | Ex vivo progenitor and stem cell expansion for usein the treatment of disease of endodermally- deri ved organs |
ITRM20030395A1 (it) | 2003-08-12 | 2005-02-13 | Istituto Naz Per Le Malattie Infettive Lazz | Terreno di coltura per il mantenimento, la proliferazione e il differenziamento di cellule di mammifero. |
WO2005017117A2 (en) | 2003-08-14 | 2005-02-24 | Martin Haas | Multipotent amniotic fetal stem cells (mafsc) and banking of same |
US7157275B2 (en) * | 2003-08-15 | 2007-01-02 | Becton, Dickinson And Company | Peptides for enhanced cell attachment and growth |
EP1670900A4 (en) * | 2003-08-27 | 2008-06-11 | Stemcells California Inc | ENHANCED PANCREATIC STEM CELL AND PRECURSOR CELL POPULATIONS AND METHOD OF IDENTIFYING, INSULATING AND ENRICHING SUCH POPULATIONS |
WO2005058301A1 (en) | 2003-12-17 | 2005-06-30 | Allergan, Inc. | Methods for treating retinoid responsive disorders using selective inhibitors of cyp26a and cyp26b |
US20060030042A1 (en) * | 2003-12-19 | 2006-02-09 | Ali Brivanlou | Maintenance of embryonic stem cells by the GSK-3 inhibitor 6-bromoindirubin-3'-oxime |
US20050266554A1 (en) | 2004-04-27 | 2005-12-01 | D Amour Kevin A | PDX1 expressing endoderm |
CN1946838A (zh) | 2003-12-23 | 2007-04-11 | 赛瑟拉公司 | 定形内胚层 |
CN103898047B (zh) * | 2003-12-23 | 2020-03-03 | 维亚希特公司 | 定形内胚层 |
US7625753B2 (en) | 2003-12-23 | 2009-12-01 | Cythera, Inc. | Expansion of definitive endoderm cells |
US7541185B2 (en) | 2003-12-23 | 2009-06-02 | Cythera, Inc. | Methods for identifying factors for differentiating definitive endoderm |
WO2005065354A2 (en) | 2003-12-31 | 2005-07-21 | The Burnham Institute | Defined media for pluripotent stem cell culture |
TWI334443B (en) * | 2003-12-31 | 2010-12-11 | Ind Tech Res Inst | Method of single cell culture of undifferentiated human embryonic stem cells |
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 |
US7794704B2 (en) | 2004-01-23 | 2010-09-14 | Advanced Cell Technology, Inc. | Methods for producing enriched populations of human retinal pigment epithelium cells for treatment of retinal degeneration |
WO2005080551A2 (en) | 2004-02-12 | 2005-09-01 | University Of Newcastle Upon Tyne | Stem cells |
US7964401B2 (en) | 2004-02-19 | 2011-06-21 | Kyoto University | Screening method for somatic cell nuclear reprogramming substance affecting ECAT2 and ECAT3 |
AU2005221095A1 (en) | 2004-03-09 | 2005-09-22 | John J. O'neil | Methods for generating insulin-producing cells |
CN1950498A (zh) | 2004-03-10 | 2007-04-18 | 加利福尼亚大学董事会 | 培养胚胎干细胞的组合物和方法 |
JP4688793B2 (ja) | 2004-03-23 | 2011-05-25 | 敏宏 赤池 | 多能性幹細胞の増殖方法 |
WO2005097980A2 (en) | 2004-03-26 | 2005-10-20 | Geron Corporation | New protocols for making hepatocytes from embryonic stem cells |
JP4491014B2 (ja) | 2004-04-01 | 2010-06-30 | ウイスコンシン アラムニ リサーチ ファンデーション | 幹細胞の内胚葉および膵臓系統への分化 |
EP1740612B1 (en) | 2004-04-27 | 2019-08-07 | Viacyte, Inc. | Pdx1 expressing endoderm |
EP1786896B1 (en) | 2004-07-09 | 2018-01-10 | Viacyte, Inc. | Methods for identifying factors for differentiating definitive endoderm |
MX2007001772A (es) | 2004-08-13 | 2007-07-11 | Univ Georgia Res Found | Composiciones y metodos para auto-renovacion y diferenciacion de celulas troncales embrionicas humanas. |
WO2006026473A2 (en) | 2004-08-25 | 2006-03-09 | University Of Georgia Research Foundation, Inc. | METHODS AND COMPOSITIONS UTILIZING MYC AND GSK3ß TO MANIPULATE THE PLURIPOTENCY OF EMBRYONIC STEM CELLS |
DE102004043256B4 (de) | 2004-09-07 | 2013-09-19 | Rheinische Friedrich-Wilhelms-Universität Bonn | Skalierbarer Prozess zur Kultivierung undifferenzierter Stammzellen in Suspension |
WO2006029198A2 (en) * | 2004-09-08 | 2006-03-16 | Wisconsin Alumni Research Foundation | Culturing human embryonic stem cells |
US7449334B2 (en) | 2004-09-08 | 2008-11-11 | Wisconsin Alumni Research Foundation | Medium containing pipecholic acid and gamma amino butyric acid and culture of embryonic stem cells |
EP1853698A1 (en) | 2005-01-28 | 2007-11-14 | NovaThera Ltd. | Methods for embryonic stem cell culture |
EP1859026A2 (en) | 2005-01-31 | 2007-11-28 | ES Cell International Pte Ltd. | Directed differentiation of embryonic stem cells and uses thereof |
US20060182724A1 (en) | 2005-02-15 | 2006-08-17 | Riordan Neil H | Method for expansion of stem cells |
PL1860950T3 (pl) | 2005-03-04 | 2017-09-29 | Lifescan, Inc. | Dojrzałe komórki podścieliska pochodzenia trzustkowego |
GB0505970D0 (en) | 2005-03-23 | 2005-04-27 | Univ Edinburgh | Culture medium containing kinase inhibitor, and uses thereof |
US7998938B2 (en) | 2005-04-15 | 2011-08-16 | Geron Corporation | Cancer treatment by combined inhibition of proteasome and telomerase activities |
CN100425694C (zh) | 2005-04-15 | 2008-10-15 | 北京大学 | 诱导胚胎干细胞向胰腺细胞分化的方法 |
US20080227656A1 (en) | 2005-04-26 | 2008-09-18 | Flemming Besenbacher | Biosurface Structure Array |
WO2006126574A1 (ja) | 2005-05-24 | 2006-11-30 | Kumamoto University | Es細胞の分化誘導方法 |
AU2006202209B2 (en) | 2005-05-27 | 2011-04-14 | Lifescan, Inc. | Amniotic fluid derived cells |
CN101238129A (zh) | 2005-06-10 | 2008-08-06 | Irm责任有限公司 | 维持胚胎干细胞多能性的化合物 |
WO2006138433A2 (en) | 2005-06-14 | 2006-12-28 | The Regents Of The University Of California | Induction of cell differentiation by class i bhlh polypeptides |
WO2006137787A1 (en) | 2005-06-21 | 2006-12-28 | Ge Healthcare Bio-Sciences Ab | Method for cell culture |
CA2613369C (en) | 2005-06-22 | 2020-11-10 | Geron Corporation | Suspension culture of human embryonic stem cells |
JP5345388B2 (ja) | 2005-06-30 | 2013-11-20 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | 環式アニリノ−ピリジノトリアジン |
WO2007012144A1 (en) | 2005-07-29 | 2007-02-01 | Australian Stem Cell Centre Limited | Compositions and methods for growth of pluripotent cells |
US20080194021A1 (en) | 2005-07-29 | 2008-08-14 | Mays Robert W | Use of a Gsk-3 Inhibitor to Maintain Potency of Culture Cells |
WO2007025234A2 (en) | 2005-08-26 | 2007-03-01 | The Trustees Of Columbia University In The City Of New York | Generation of pancreatic endocrine cells from primary duct cell cultures and methods of use for treatment of diabetes |
WO2007026353A2 (en) | 2005-08-29 | 2007-03-08 | Technion Research & Development Foundation Ltd. | Media for culturing stem cells |
WO2007027157A1 (en) | 2005-09-02 | 2007-03-08 | Agency For Science, Technology And Research | Method of deriving progenitor cell line |
GB2444686B (en) | 2005-09-12 | 2010-08-25 | Es Cell Int Pte Ltd | Differentiation of pluripotent stem cells using p38 MAPK inhibitors or prostaglandins |
JP2009511061A (ja) | 2005-10-14 | 2009-03-19 | リージェンツ オブ ザ ユニバーシティ オブ ミネソタ | 膵臓表現型を有する細胞への非胚性幹細胞の分化 |
US7732202B2 (en) | 2005-10-21 | 2010-06-08 | International Stem Cell Corporation | Oxygen tension for the parthenogenic activation of human oocytes for the production of human embryonic stem cells |
DK2674485T3 (da) | 2005-10-27 | 2019-08-26 | Viacyte Inc | Pdx-1 udtrykkende dorsal og ventral fortarm endoderm |
EP2206724A1 (en) | 2005-12-13 | 2010-07-14 | Kyoto University | Nuclear reprogramming factor |
WO2007082963A1 (es) | 2006-01-18 | 2007-07-26 | Fundación Instituto Valenciano De Infertilidad | Líneas de células madre embrionarias humanas y métodos para usar las mismas |
CA2643478C (en) | 2006-02-23 | 2019-06-18 | Novocell, Inc. | Compositions and methods useful for culturing differentiable cells |
DK2650360T3 (da) | 2006-03-02 | 2019-10-07 | Viacyte Inc | Endokrine prekursorceller, pancreatiske hormon udtrykkende celler og fremgangsmåder til fremstilling |
US7695965B2 (en) * | 2006-03-02 | 2010-04-13 | Cythera, Inc. | Methods of producing pancreatic hormones |
ES2725601T3 (es) | 2006-04-28 | 2019-09-25 | Lifescan Inc | Diferenciación de células madre embriónicas humanas |
US8741643B2 (en) * | 2006-04-28 | 2014-06-03 | Lifescan, Inc. | Differentiation of pluripotent stem cells to definitive endoderm lineage |
US20070259423A1 (en) | 2006-05-02 | 2007-11-08 | Jon Odorico | Method of differentiating stem cells into cells of the endoderm and pancreatic lineage |
US8685730B2 (en) | 2006-05-02 | 2014-04-01 | Wisconsin Alumni Research Foundation | Methods and devices for differentiating pluripotent stem cells into cells of the pancreatic lineage |
US9598673B2 (en) | 2006-05-19 | 2017-03-21 | Creative Medical Health | Treatment of disc degenerative disease |
WO2007139929A2 (en) | 2006-05-25 | 2007-12-06 | The Burnham Institute For Medical Research | Methods for culture and production of single cell populations of human embryonic stem cells |
CA2654196A1 (en) | 2006-06-02 | 2007-12-13 | University Of Georgia Research Foundation, Inc. | Pancreatic and liver endoderm cells and tissue by differentiation of definitive endoderm cells obtained from human embryonic stems |
CN101541953A (zh) | 2006-06-02 | 2009-09-23 | 佐治亚大学研究基金会 | 通过从人胚胎干细胞获得的定形内胚层细胞的分化得到胰和肝内胚层细胞及组织 |
US8415153B2 (en) | 2006-06-19 | 2013-04-09 | Geron Corporation | Differentiation and enrichment of islet-like cells from human pluripotent stem cells |
CN100494359C (zh) | 2006-06-23 | 2009-06-03 | 中日友好医院 | 神经干细胞三维立体培养体外扩增的方法 |
AU2007297575A1 (en) | 2006-06-26 | 2008-03-27 | Lifescan, Inc. | Pluripotent stem cell culture |
US20080003676A1 (en) | 2006-06-26 | 2008-01-03 | Millipore Corporation | Growth of embryonic stem cells |
GB2454386B (en) | 2006-07-06 | 2011-07-06 | Es Cell Int Pte Ltd | Method for embryonic stem cell culture on a positively charged support surface |
WO2008013664A2 (en) | 2006-07-26 | 2008-01-31 | Cythera, Inc. | Methods of producing pancreatic hormones |
WO2008015682A2 (en) | 2006-08-02 | 2008-02-07 | Technion Research & Development Foundation Ltd. | Methods of expanding embryonic stem cells in a suspension culture |
KR101331510B1 (ko) | 2006-08-30 | 2013-11-20 | 재단법인서울대학교산학협력재단 | 저농도의 포도당을 함유하는 인간 배아줄기세포용 배지조성물 및 이를 이용한 인간 배아 줄기세포로부터 인슐린생산 세포 또는 세포괴로 분화시키는 방법, 그리고그로부터 유도된 인슐린 생산 세포 또는 세포괴 |
JP2008099662A (ja) | 2006-09-22 | 2008-05-01 | Institute Of Physical & Chemical Research | 幹細胞の培養方法 |
WO2008039521A2 (en) * | 2006-09-26 | 2008-04-03 | Nmt Medical, Inc. | Method for modifying a medical implant surface for promoting tissue growth |
US20100323442A1 (en) | 2006-10-17 | 2010-12-23 | Emmanuel Edward Baetge | Modulation of the phosphatidylinositol-3-kinase pathway in the differentiation of human embryonic stem cells |
JP5343267B2 (ja) | 2006-10-17 | 2013-11-13 | スティーフェル・ラボラトリーズ・インコーポレーテッド | タラロゾール代謝物 |
US8835163B2 (en) | 2006-10-18 | 2014-09-16 | The Board Of Trustees Of The University Of Illinois | Embryonic-like stem cells derived from adult human peripheral blood and methods of use |
EP2088190A4 (en) | 2006-11-09 | 2011-01-05 | Japan Government | METHOD FOR THE CULTURE AND PASSAGE OF PRIMATE EMBRYONIC STRAIN CELL, AND METHOD FOR INDUCING DIFFERENTIATION OF EMBRYONIC STEM CELL |
WO2008086005A1 (en) | 2007-01-09 | 2008-07-17 | University Of South Florida | Compositions including triciribine and bortezomib and derivatives thereof and methods of use thereof |
WO2008094597A2 (en) | 2007-01-30 | 2008-08-07 | University Of Georgia Research Foundation, Inc. | Early mesoderm cells, a stable population of mesendoderm cells that has utility for generation of endoderm and mesoderm lineages and multipotent migratory cells (mmc) |
GB0703188D0 (en) | 2007-02-19 | 2007-03-28 | Roger Land Building | Large scale production of stem cells |
WO2008148105A1 (en) | 2007-05-25 | 2008-12-04 | Medistem Laboratories, Inc. | Endometrial stem cells and methods of making and using same |
DK2173863T3 (en) | 2007-06-29 | 2019-01-21 | Fujifilm Cellular Dynamics Inc | Automated method and apparatus for embryonic stem cell culture |
EP3957716A1 (en) | 2007-07-18 | 2022-02-23 | Janssen Biotech, Inc. | Differentiation of human embryonic stem cells |
CA2694956C (en) * | 2007-07-31 | 2017-12-19 | Lifescan, Inc. | Pluripotent stem cell differentiation by using human feeder cells |
RU2473685C2 (ru) | 2007-07-31 | 2013-01-27 | Лайфскен, Инк. | Дифференцировка человеческих эмбриональных стволовых клеток |
MX2010002179A (es) | 2007-08-24 | 2010-04-27 | Stichting Het Nl Kanker I | Composicion para el tratamiento de enfermedades neoplasicas. |
WO2009061442A1 (en) | 2007-11-06 | 2009-05-14 | Children's Medical Center Corporation | Method to produce induced pluripotent stem (ips) cells form non-embryonic human cells |
SG154367A1 (en) | 2008-01-31 | 2009-08-28 | Es Cell Int Pte Ltd | Method of differentiating stem cells |
WO2009096049A1 (ja) | 2008-02-01 | 2009-08-06 | Kyoto University | 人工多能性幹細胞由来分化細胞 |
EP2250252A2 (en) | 2008-02-11 | 2010-11-17 | Cambridge Enterprise Limited | Improved reprogramming of mammalian cells, and the cells obtained |
BR122017025207B1 (pt) | 2008-02-21 | 2021-03-16 | Centocor Ortho Biotech Inc | superfície que faz parte de um recipiente ou matriz destinada para uso em uma cultura de células ou análises, desprovida de uma camada de células alimentadoras e desprovida de uma camada adsorvente |
WO2009110215A1 (ja) | 2008-03-03 | 2009-09-11 | 独立行政法人 科学技術振興機構 | 繊毛細胞の分化誘導方法 |
JP2011514169A (ja) * | 2008-03-17 | 2011-05-06 | エージェンシー フォー サイエンス,テクノロジー アンド リサーチ | 幹細胞培養のためのマイクロキャリア |
RU2359030C1 (ru) | 2008-03-19 | 2009-06-20 | Общество С Ограниченной Ответственностью "Лаборатория Клеточных Технологий" | Способ получения эндотелиальных клеток из эмбриональных стволовых клеток человека (варианты) |
AU2008355123B2 (en) | 2008-04-21 | 2014-12-04 | Viacyte, Inc. | Methods for purifying endoderm and pancreatic endoderm cells derived from human embryonic stem cells |
US8338170B2 (en) | 2008-04-21 | 2012-12-25 | Viacyte, Inc. | Methods for purifying endoderm and pancreatic endoderm cells derived from human embryonic stem cells |
US7939322B2 (en) | 2008-04-24 | 2011-05-10 | Centocor Ortho Biotech Inc. | Cells expressing pluripotency markers and expressing markers characteristic of the definitive endoderm |
US8623648B2 (en) | 2008-04-24 | 2014-01-07 | Janssen Biotech, Inc. | Treatment of pluripotent cells |
US20090298178A1 (en) | 2008-06-03 | 2009-12-03 | D Amour Kevin Allen | Growth factors for production of definitive endoderm |
DK2297319T3 (en) | 2008-06-03 | 2015-10-19 | Viacyte Inc | GROWTH FACTORS FOR PREPARING DEFINITIVE ENDODERM |
DE102008032236A1 (de) | 2008-06-30 | 2010-04-01 | Eberhard-Karls-Universität Tübingen | Isolierung und/oder Identifizierung von Stammzellen mit adipozytärem, chondrozytärem und pankreatischem Differenzierungspotential |
CA2729121C (en) | 2008-06-30 | 2019-04-09 | Centocor Ortho Biotech Inc. | Differentiation of pluripotent stem cells |
US20100028307A1 (en) | 2008-07-31 | 2010-02-04 | O'neil John J | Pluripotent stem cell differentiation |
US9683215B2 (en) | 2008-08-22 | 2017-06-20 | President And Fellows Of Harvard College | Methods of reprogramming cells |
US9012218B2 (en) | 2008-10-31 | 2015-04-21 | Janssen Biotech, Inc. | Differentiation of human embryonic stem cells |
RU2522001C2 (ru) | 2008-10-31 | 2014-07-10 | Сентокор Орто Байотек Инк. | Дифференцирование человеческих эмбриональных стволовых клеток в линию панкреатических эндокринных клеток |
EP2356213B1 (en) | 2008-11-04 | 2019-05-29 | Viacyte, Inc. | Stem cell aggregate suspension compositions and methods for differentiation thereof |
US8008075B2 (en) | 2008-11-04 | 2011-08-30 | Viacyte, Inc. | Stem cell aggregate suspension compositions and methods of differentiation thereof |
US8278106B2 (en) | 2008-11-14 | 2012-10-02 | Viacyte, Inc. | Encapsulation of pancreatic cells derived from human pluripotent stem cells |
CN107267442A (zh) | 2008-11-20 | 2017-10-20 | 詹森生物科技公司 | 微载体上的多能干细胞培养 |
US20110229441A1 (en) | 2008-12-05 | 2011-09-22 | Association Francaise Contre Les Myopathies | Method and Medium for Neural Differentiation of Pluripotent Cells |
AU2010276402B2 (en) | 2009-07-20 | 2014-07-03 | Janssen Biotech, Inc. | Differentiation of human embryonic stem cells |
KR20170118969A (ko) | 2009-07-20 | 2017-10-25 | 얀센 바이오테크 인코포레이티드 | 인간 배아 줄기 세포의 분화 |
CA2778817A1 (en) | 2009-10-29 | 2011-05-19 | Janssen Biotech, Inc. | Pluripotent stem cells |
FI20096288A0 (fi) | 2009-12-04 | 2009-12-04 | Kristiina Rajala | Formulations and methods for culturing stem cells |
AU2010333840B2 (en) | 2009-12-23 | 2016-01-07 | Janssen Biotech, Inc. | Differentiation of human embryonic stem cells |
BR112012017761A2 (pt) | 2009-12-23 | 2015-09-15 | Centocor Ortho Biotech Inc | diferenciação das células-tronco embrionárias humanas |
CA2785966C (en) | 2009-12-29 | 2020-10-27 | Takeda Pharmaceutical Company Limited | Method for manufacturing pancreatic-hormone-producing cells |
WO2011096223A1 (ja) | 2010-02-03 | 2011-08-11 | 独立行政法人国立がん研究センター | 誘導肝幹細胞及びその製造方法、並びに、該細胞の応用 |
SG183400A1 (en) | 2010-03-02 | 2012-09-27 | Univ Singapore | Culture additives to boost stem cell proliferation and differentiation response |
CA2800498C (en) | 2010-03-31 | 2021-11-16 | The Scripps Research Institute | Reprogramming cells |
US9234170B2 (en) | 2010-04-25 | 2016-01-12 | Mount Sinai School Of Medicine | Generation of anterior foregut endoderm from pluripotent cells |
JP6050225B2 (ja) | 2010-05-12 | 2016-12-21 | 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 |
WO2011160066A1 (en) | 2010-06-17 | 2011-12-22 | Regents Of The University Of Minnesota | Production of insulin producing cells |
SG187699A1 (en) | 2010-08-05 | 2013-03-28 | Wisconsin Alumni Res Found | Simplified basic media for human pluripotent cell culture |
EP2611910B1 (en) | 2010-08-31 | 2018-01-17 | Janssen Biotech, Inc. | Differentiation of human embryonic stem cells |
ES2585028T3 (es) | 2010-08-31 | 2016-10-03 | Janssen Biotech, Inc. | Diferenciación de células madre pluripotentes |
WO2012117333A1 (en) | 2011-02-28 | 2012-09-07 | Stempeutics Research Malaysia Sdn Bhd | Isolation and expansion of adult stem cells, their therapeutic composition and uses thereof |
WO2013055834A2 (en) | 2011-10-11 | 2013-04-18 | The New York Stem Cell Foundation | Er stress relievers in beta cell protection |
WO2013055397A1 (en) | 2011-10-14 | 2013-04-18 | Children's Medical Center Corporation | Inhibition and enhancement of reprogramming by chromatin modifying enzymes |
SG11201403473QA (en) | 2011-12-22 | 2014-10-30 | Janssen Biotech Inc | Differentiation of human embryonic stem cells into single hormonal insulin positive cells |
US10519422B2 (en) | 2012-02-29 | 2019-12-31 | Riken | Method of producing human retinal pigment epithelial cells |
KR102114209B1 (ko) | 2012-06-08 | 2020-05-25 | 얀센 바이오테크 인코포레이티드 | 인간 배아 줄기 세포의 췌장 내분비 세포로의 분화 |
JP6470687B2 (ja) | 2012-09-03 | 2019-02-13 | ノヴォ ノルディスク アー/エス | 小分子を用いた多能性幹細胞からの膵臓内胚葉の作製 |
CN111394298A (zh) | 2012-12-31 | 2020-07-10 | 詹森生物科技公司 | 使用hb9调节子使人胚胎干细胞分化为胰腺内分泌细胞的方法 |
US8859286B2 (en) | 2013-03-14 | 2014-10-14 | Viacyte, Inc. | In vitro differentiation of pluripotent stem cells to pancreatic endoderm cells (PEC) and endocrine cells |
WO2014152321A1 (en) | 2013-03-15 | 2014-09-25 | The Jackson Laboratory | Isolation of non-embryonic stem cells and uses thereof |
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Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2011504753A (ja) * | 2007-11-27 | 2011-02-17 | ライフスキャン・インコーポレイテッド | ヒト胚性幹細胞の分化 |
WO2009132083A2 (en) * | 2008-04-22 | 2009-10-29 | President And Fellows Of Harvard College | Compositions and methods for promoting the generation of pdx1+ pancreatic cells |
Non-Patent Citations (12)
Title |
---|
JPN6014047904; Development Vol.125, 1998, p.4863-4876 * |
JPN6014047906; Development Vol.129, 2002, p.4685-4696 * |
JPN6014047908; Development Vol.126, 1999, p.723-732 * |
JPN6014047909; J.Hepatol. Author Manuscript Vol.49, No.3, 200901, p.384-395 * |
JPN6014047911; Development Vol.129, 2002, p.1819-1828 * |
JPN6014047912; Developmental Dynamics Vol.238, Issue 12, 200910, p.3035-3042 * |
JPN6015006899; Stem Cells Dev.,2007,16(4),p.561-78 * |
JPN6015006914; Nat.Biotechnol.,2006,24(11),p.1392-401 * |
JPN6015006915; J.Endocrinol.,2005,186(2),p.343-52 * |
JPN6015048994; 成島 道樹ら: 'A human beta-cell line for transplantation therapy to control type 1 diabetes' 岡山医学会雑誌 Vol. 119, No. 1, 200705, P11-16 * |
JPN6015048995; 永井敏雄ら: '各種心筋組織幹細胞の類似点と相違点' 分子心血管病 Vol.8, No.3, 200706, p.240-246 * |
JPN6015048996; 武藤弘行: '消化管の発生・分化と転写因子' G.I.Research Vol.7, No.4, 1999, p.239-247 * |
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