JP6080777B2 - 細胞培養のための合成被覆 - Google Patents
細胞培養のための合成被覆 Download PDFInfo
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- JP6080777B2 JP6080777B2 JP2013558028A JP2013558028A JP6080777B2 JP 6080777 B2 JP6080777 B2 JP 6080777B2 JP 2013558028 A JP2013558028 A JP 2013558028A JP 2013558028 A JP2013558028 A JP 2013558028A JP 6080777 B2 JP6080777 B2 JP 6080777B2
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- 150000004053 quinones Chemical class 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 235000016491 selenocysteine Nutrition 0.000 description 1
- 125000001554 selenocysteine group Chemical class [H][Se]C([H])([H])C(N([H])[H])C(=O)O* 0.000 description 1
- 150000003346 selenoethers Chemical class 0.000 description 1
- 229910000077 silane Inorganic materials 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 210000002363 skeletal muscle cell Anatomy 0.000 description 1
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
- 239000005361 soda-lime glass Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000007480 spreading Effects 0.000 description 1
- 238000003892 spreading Methods 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- YRHRIQCWCFGUEQ-UHFFFAOYSA-N thioxanthen-9-one Chemical compound C1=CC=C2C(=O)C3=CC=CC=C3SC2=C1 YRHRIQCWCFGUEQ-UHFFFAOYSA-N 0.000 description 1
- 210000003014 totipotent stem cell Anatomy 0.000 description 1
- 229940099456 transforming growth factor beta 1 Drugs 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 210000005167 vascular cell Anatomy 0.000 description 1
- 229920003176 water-insoluble polymer Polymers 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 1
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- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09D—COATING COMPOSITIONS, e.g. PAINTS, VARNISHES OR LACQUERS; FILLING PASTES; CHEMICAL PAINT OR INK REMOVERS; INKS; CORRECTING FLUIDS; WOODSTAINS; PASTES OR SOLIDS FOR COLOURING OR PRINTING; USE OF MATERIALS THEREFOR
- C09D151/00—Coating compositions based on graft polymers in which the grafted component is obtained by reactions only involving carbon-to-carbon unsaturated bonds; Coating compositions based on derivatives of such polymers
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
- B05D—PROCESSES FOR APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
- B05D3/00—Pretreatment of surfaces to which liquids or other fluent materials are to be applied; After-treatment of applied coatings, e.g. intermediate treating of an applied coating preparatory to subsequent applications of liquids or other fluent materials
- B05D3/06—Pretreatment of surfaces to which liquids or other fluent materials are to be applied; After-treatment of applied coatings, e.g. intermediate treating of an applied coating preparatory to subsequent applications of liquids or other fluent materials by exposure to radiation
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- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09D—COATING COMPOSITIONS, e.g. PAINTS, VARNISHES OR LACQUERS; FILLING PASTES; CHEMICAL PAINT OR INK REMOVERS; INKS; CORRECTING FLUIDS; WOODSTAINS; PASTES OR SOLIDS FOR COLOURING OR PRINTING; USE OF MATERIALS THEREFOR
- C09D189/00—Coating compositions based on proteins; Coating compositions based on derivatives thereof
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F220/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical or a salt, anhydride ester, amide, imide or nitrile thereof
- C08F220/02—Monocarboxylic acids having less than ten carbon atoms; Derivatives thereof
- C08F220/10—Esters
- C08F220/20—Esters of polyhydric alcohols or phenols, e.g. 2-hydroxyethyl (meth)acrylate or glycerol mono-(meth)acrylate
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F220/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical or a salt, anhydride ester, amide, imide or nitrile thereof
- C08F220/02—Monocarboxylic acids having less than ten carbon atoms; Derivatives thereof
- C08F220/10—Esters
- C08F220/26—Esters containing oxygen in addition to the carboxy oxygen
- C08F220/28—Esters containing oxygen in addition to the carboxy oxygen containing no aromatic rings in the alcohol moiety
- C08F220/285—Esters containing oxygen in addition to the carboxy oxygen containing no aromatic rings in the alcohol moiety and containing a polyether chain in the alcohol moiety
- C08F220/286—Esters containing oxygen in addition to the carboxy oxygen containing no aromatic rings in the alcohol moiety and containing a polyether chain in the alcohol moiety and containing polyethylene oxide in the alcohol moiety, e.g. methoxy polyethylene glycol (meth)acrylate
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- Peptides Or Proteins (AREA)
- Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)
Description
ここに記載されたポリペプチドに接続したポリマーは、室温で水溶性である。しかしながら、多くの実施の形態において、ポリペプチドに接続していない実質的に類似のポリマーは、室温で水溶性ではない。そのような実施の形態において、ポリペプチドは、ポリペプチドに接続したポリマーを水溶性にする働きをする。ポリペプチドに接続していない実質的に類似のポリマーは、典型的に37℃である細胞培養温度で水溶性ではないことが好ましい。細胞培養のための適切なモジュラスを提供するために、ポリマーが、37℃で水中において膨潤性であることも望ましい。
ポリペプチドは、どのような適切な様式でポリマーに接続してもよい。いくつかの実施の形態において、モノマーは、ポリペプチドを含むように誘導体化されており、それゆえ、ポリペプチドは、ポリマーが形成されているときにポリマーに取り込まれる。いくつかの実施の形態において、ポリペプチドは、ポリマーが形成された後にポリマーにグラフトされる。
ポリペプチドに接続したポリマーは、細胞培養物品を被覆するのに使用するために、水溶液中に溶解されていてもよい。この水溶液は、有機溶媒を含まない、または実質的に含まない。いくらかの少量の有機溶媒が、例えば、重合後のポリマー中に残留するいくらかの有機溶媒の結果として、水溶液中に存在するかもしれないと理解されるであろう。ここに用いたように、「実質的に含まない」は、水溶液中の有機溶媒に関するように、水溶液が有機溶媒を2質量%未満しか含まないことを意味する。多くの実施の形態において、水溶液は、1%未満、0.5%未満、0.2%未満、または0.1%未満しか有機溶媒を含有しない。水溶液が含まない有機溶媒の例としては、メタノール、エタノール、ブタノール、プロパノール、オクタノール、ヘキサン、ヘプタン、アセトン、酢酸アセチル、酢酸エチル、ジメチルホルムアミド(DMF)、ジメチルスルホキシド(DMSO)などが挙げられる。
ポリペプチドに接続したポリマーは、どのような適切な様式で細胞培養物品に被覆してもよい。一般に、先に記載したような、ポリペプチドに接続したポリマーを含有する水溶液は、細胞培養物品の表面上に配置される。その水溶液は、その物品の表面に吹き付けても、または物品の表面に注ぐなどしてもよい。いくつかの実施の形態において、その物品は、水溶液に沈められ、そこから取り出される。
ここに記載されたポリペプチドに接続したポリマーは、6,12,96,384および1536ウェルプレートなどのシングルおよびマルチウェルプレート、瓶、ペトリ皿、フラスコ、ビーカー、プレート、ローラーボトル、区画および多区画培養スライドなどのスライド、試験管、カバースリップ、バッグ、膜、中空繊維、ビーズおよびマイクロキャリア、カップ、スピナーボトル、潅流チャンバ、バイオリアクタ、CellSTACK(登録商標)および発酵槽などの任意の適切な細胞培養物品の表面に結合させてもよい。
上述したような接続したポリペプチドを含有するポリマーを有する細胞培養物品に細胞を播種してよい。細胞はどのような細胞タイプのものであってもよい。例えば、細胞は、上皮細胞、内皮細胞、骨格筋細胞、平滑筋細胞、心筋細胞、腸細胞、肝細胞、または他の臓器からの細胞、幹細胞、島細胞、血管細胞、白血球、癌細胞などの結合組織細胞であってよい。細胞は、哺乳類細胞、好ましくはヒト細胞であってよいが、細菌、酵母、または植物細胞などの非哺乳類細胞であってもよい。
第1の態様において、細胞培養物品の表面を被覆する方法は、共有結合したポリペプチドを有するポリマーを水溶液中に溶解させて、ポリマー溶液を生成する工程を含む。このポリマーは、二価以上の官能性を有するモノマーからは作られない。ポリペプチドに接続したポリマーに対するポリペプチドの質量百分率は、ポリペプチドに接続したポリマーを水溶性にするほど十分に高い。この水溶液は有機溶媒を実質的に含まない。この方法は、(i)細胞培養物品の表面にポリマー溶液を配置して、被覆物品を製造する工程、および(ii)被覆物品に、ポリペプチドに接続したポリマーを細胞培養物品の表面に結合させるのに十分な熱または電磁放射線を施す工程をさらに含む。
メタクリル酸−(ポリエチレングリコール)4−ビトロネクチン(MAA−PEG4−VN)は、カリフォルニア州サニーベール所在のAmerican Peptide社により提供され、以下のように合成された。VNポリペプチド配列は、KGGPQVTRGDVFTMP(配列番号1)であった。
撹拌子を備えた琥珀色のフラスコ内の7.5mlのエタノールに、ヒドロキシエチルメタクリレート(HEMA)、60mg(0.46ミリモル)およびMAA−PEO4−VN、100mg(0.05ミリモル)を加えた。次いで、2,2’−アゾビス−(2−メチルブチロニトリル)、9mgを加え、完全に溶解するまで撹拌した。1分間に亘るアルゴンのパージにより、この溶液から酸素を除去した。次いで、密封したフラスコを、混合しながら68℃で24時間に亘り加熱し、光から守った。室温に冷却した後、酢酸エチル中に粗製反応媒質を注ぎ入れることによって、ポリ(HEMA−co−MAA−PEO4−VN)を単離した。得られた白色固体をジイソプロピルエーテルで3回洗浄し、凍結乾燥した。
10mlの脱イオン(DI)水中に2.5mgのポリ(HEMA−co−MAA−PEO4−VN)ポリマーを溶解させることによって、被覆組成物を調製した。この溶液は、使用前に4℃で貯蔵することができる。
超低接着表面(ULA)処理し、組織培養処理(TCT)し、「CellBIND」処理したポリスチレン(PS)プレートについて、6ウェルプレートの各ウェル内に、800μlの被覆組成物を分配した。非処理ポリスチレンプレートの場合、6ウェルプレートの各ウェル内に、2mlの被覆組成物を分配した。次いで、これらのプレートを、6時間に亘り37℃のインキュベータ内、または15分間に亘り80℃のオーブン内に配置した、もしくはフュージョン「D」バルブにより与えられる30J/cm2のUV光線量に曝露した。次いで、過剰の被覆組成物を吸引した。これらのプレートを、1%のドデシル硫酸ナトリウム(SDS)水溶液で1時間に亘り洗浄し、その後、DI水で濯ぎ、乾燥空気流で乾燥させた。これらのプレートは、消毒または殺菌の準備ができていた。
1×106のBG01vヒト胚幹細胞(hESC)、35継代を、6ウェルプレートの3つのウェルの各々に播種し、37℃でインキュベーションした。1つのプレートは上述したように被覆されたウェルを含み、別のプレートは、製造業者の使用説明書にしたがって、「Matrigel」被覆:BD「Matrigel」ロット番号A5628(BD Bioscienceカタログ#356231)で被覆された。これらのプレートを、播種前に、水中70%v/vのエタノールとインキュベーションすることによって消毒した。細胞は既知組成培地:「mTeSR1」培地(StemCell Technologiesカタログ#05850)において、ウェル当たり4ml、1回の播種(2日間)で培養した。
70,000の骨髄由来ヒト間葉系幹細胞(hMSC)(StemCell Technologiesカタログ#MSC−001F)、4継代を、6ウェルプレートの各ウェルに播種し、37℃でインキュベーションした。1つのプレートは、上述したようにポリマーポリペプチドに被覆された(UV、30J/cm2)ウェルを含み、別のプレートは、製造業者の使用説明書にしたがって、「MesenCult」−XF Attachment Substrate(StemCell Technologiesカタログ#05424−1:1×DPBS中の28希釈)で被覆され、さらに別のプレートは、コーニング社の「Synthemax」合成基体で被覆された。細胞は既知組成培地:「MesenCult」−XF培地(StemCell Technologiesカタログ#05420)において、ウェル当たり3ml、1回の播種(2日間)で培養した。細胞は、0.05%トリプシン−EDTA溶液(Gibco/Invitrogen、カタログ#25300)による酵素消化により4日目に収穫し、計数した。
ES−D3細胞(ATCC# CRL−11632)を、カリフォルニア州カールズバッド所在のATCCにより推奨されるように、15%のFBSおよび0.1mMのベータ−メルカプトエタノールを補った、カリフォルニア州カールズバッド所在のLife Technologies社のダルベッコ改変イーグル培地中で増殖させた。細胞をトリプシン処理し、それらが飽和密度に到達する前に、希釈した。次いで、細胞を計数し、D−PBS中で洗浄し、「mTeSR1」合成培地(カナダ国、ブリティッシュコロンビア州バンクーバー所在のStem Cell Technologies社)中に再懸濁させた。次いで、ウェル当たり7×105の細胞を、6ウェルプレートのフォーマットで2mlの「mTeSR1」中に単細胞として播種し、37℃でインキュベーションした。
15 表面
20 ポリマー
30 中間層
50 ウェル
55 側壁
70 ポリペプチド
80 リンカー
100 細胞培養物品
Claims (5)
- 細胞培養物品の表面を被覆する方法において、
共有結合したポリペプチドを有するポリマーを、有機溶媒を実質的に含まない水溶液中に溶解させて、ポリマー溶液を生成する工程であって、前記ポリマーは、(i)前記ポリペプチドに結合したメタクリル酸と(ii)ヒドロキシエチルメタクリレートとの重合により形成されたものであり、かつ架橋を含まず、前記ポリペプチドに結合したポリマーに対するポリペプチドの質量百分率が40%以上である工程、
細胞培養物品の表面に前記ポリマー溶液を配置して、被覆物品を製造する工程、および
前記被覆物品を室温から80℃の温度でインキュベーションして、または電磁放射線を施して、前記ポリペプチドに結合したポリマーを前記細胞培養物品の表面に結合させる工程、
を有してなる方法。 - 被覆された細胞培養物品であって、該細胞培養物品の表面に結合した、共有結合したポリペプチドを有するポリマーを含み、
前記ポリマーは、(i)前記ポリペプチドに結合したメタクリル酸と(ii)ヒドロキシエチルメタクリレートとの重合体であり、かつ架橋を含まず、
前記ポリペプチドに結合したポリマーに対する前記ポリペプチドの質量百分率が40%以上である、細胞培養物品。 - 細胞培養物品の表面を被覆するための組成物であって、
共有結合したポリペプチドを有するポリマーを含み、
前記ポリマーが、(i)前記ポリペプチドに結合したメタクリル酸と(ii)ヒドロキシエチルメタクリレートとの重合体であり、かつ架橋を含まず、
前記ポリペプチドに結合したポリマーに対する前記ポリペプチドの質量百分率が40%以上である、組成物。 - 水溶液をさらに含み、前記ポリマーが該水溶液中に溶解している、請求項3記載の組成物。
- 有機溶媒を実質的に含まない、請求項4記載の組成物。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201161453654P | 2011-03-17 | 2011-03-17 | |
US61/453,654 | 2011-03-17 | ||
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