JPH10503923A - エクスビボのヒト胎児膵臓細胞及びヒト成人膵臓細胞の増殖及び分化を刺激する組成物及び方法 - Google Patents
エクスビボのヒト胎児膵臓細胞及びヒト成人膵臓細胞の増殖及び分化を刺激する組成物及び方法Info
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- JPH10503923A JPH10503923A JP7528510A JP52851095A JPH10503923A JP H10503923 A JPH10503923 A JP H10503923A JP 7528510 A JP7528510 A JP 7528510A JP 52851095 A JP52851095 A JP 52851095A JP H10503923 A JPH10503923 A JP H10503923A
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Abstract
Description
Claims (1)
- 【特許請求の範囲】 1.(a)ヒト膵臓細胞の初代培養を調製する段階、及び (b)該初代培養細胞を有効濃度のHGF/SFと有効な時間接触させる段階、 を含む、ヒト膵臓β膵島細胞のエクスビボの増殖及び分化を刺激する方法。 2.初代培養細胞を有効濃度の抗−TGF−β抗体と有効な時間接触させること をさらに含む、請求の範囲1の方法。 3.ヒト膵臓細胞が胎児膵臓細胞である、請求の範囲1の方法。 4.ヒト膵臓細胞が成熟膵臓細胞である、請求の範囲1の方法。 5.細胞増殖が他の細胞型に対するβ上皮細胞数の増加を含む、請求の範囲1の 方法。 6.細胞分化がβ上皮細胞を含有する膵島様細胞クラスターの形成の増加を含む 、請求の範囲1の方法。 7.細胞増殖及び分化が平均細胞インスリン産生の増加を含む、請求の範囲1の 方法。 8.HGF/SFの該有効濃度が約5から約50ng/mlまでの範囲である、請求 の範囲1の方法。 9.培養された細胞をHGF/SFの存在下で細胞外マトリックス上で単層で培 養することをさらに含む、請求の範囲1の方法。 10.細胞外マトリックスが804G細胞外マトリックスである、請求の範囲9 の方法。 11.細胞外マトリックスがBCEM細胞外マトリックスである、請求の範囲9 の方法。 12.単層培養細胞を再集合させることをさらに含む、請求の範囲9の方法。 13.細胞をインスリン遺伝子を促進制御する試薬と接触させることをさらに含 む、請求の範囲1、9又は12のいずれかの方法。 14.試薬がポリ(ADP−リボース)合成酵素阻害剤である、請求の範囲13 の方法。 15.阻害剤がニコチンアミド又はベンズアミドである、請求の範囲14の方法 。 16.(a)ヒト膵臓細胞の初代培養を調製する段階、 (b)該細胞を、膵島細胞クラスターが形成する条件下で有効濃度のHGF/S Fと共に培養する段階、 (c)該クラスターを、有効濃度のHGF/SFの存在下で細胞外マトリックス 上の単層として培養する段階、 (d)該細胞を、非酵素的手段により該単層から解離する段階、及び (e)該解離された細胞を、ポリ(ADP−リボース)合成酵素の阻害剤の存 在下で再集合させる段階、 を含む、ヒト胎児膵臓β細胞のエクスビボの増殖及び分化を刺激する方法。 17.(a)ヒト胎児膵臓細胞の初代培養を調製する段階、 (b)増加したインスリンを産生するβ上皮細胞を含有する膵島様細胞クラス ターが初代培養から生成するように、該培養を有効濃度のHGF/SFを含む試 薬と有効な時間接触させ;場合により有効濃度の抗―TGF―β抗体と接触させ る段階; (c)上記のように処理した胎児膵臓細胞を回収する段階、及び (d)有効量の上記(c)項の細胞を患者に非経口的に移植する段階、 を含む、1型糖尿病の患者を治療する方法。 18.非経口的移植が、門脈内経路、脾臓内経路、腎被膜下経路、又は静脈内経 路による投与を含む、請求の範囲17の方法。 19.段階(b)が、有効濃度のHGF/SFの存在下で細胞外マトリックス上 の単層培養で細胞を培養することをさらに含む、請求の範囲17の方法。 20.細胞外マトリックスが804G又はBCEMである、請求の範囲19の方 法。 21.非酵素的手段により単層細胞をマトリックスから解離し、次に該解離され た細胞を再集合させることをさらに含む、請求の範囲19の方法。 22.再集合した細胞を、該細胞中のインスリン遺伝子を促進制御する試薬と接 触させることをさらに含む、請求の範囲21の方法。 23.試薬がポリ(ADP−リボース)合成酵素阻害剤である、請求の範囲22 の方法。 24.阻害剤がニコチンアミド又はベンズアミドである、請求の範囲23の方法 。 25.(a)バイオリアクターにヒト膵臓細胞培養物を接種する段階、 (b)該バイオリアクターを、場合により有効濃度の抗―TGF―β抗体と共に 、有効濃度のHGF/SFを添加した完全増殖培地で灌流する段階、及び (c)該バイオリアクターから、β上皮細胞を含有する膵島様細胞クラスターを 回収する段階、 を含む、臨床的に有用な量の増殖し分化するヒト胎児膵島細胞を製造する方法。 26.(a)クラスターを、培養表面が細胞外マトリックスで被覆されている第 2のバイオリアクターに接種する段階、 (b)有効濃度のHGF/SF及び場合により有効濃度の抗―TGF―β抗体を 添加した増殖培地で、該第2のバイオリアクターを灌流する段階、 (c)該マトリックスから非酵素的手段により細胞を解離する段階、 (d)該解離した細胞を再集合させる段階、及び (e)該再集合した細胞を、インスリン遺伝子促進制御剤と接触させる段階、 をさらに含む、請求の範囲25の方法。 27.有効濃度のHGF/SFの存在下で、場合により有効濃度の抗―TGF― β抗体の存在下で懸濁培養中又は細胞外マトリックス上でエクスビボで培養され 、インスリン遺伝子促進制御剤の存在下で膵臓細胞の増殖及び分化が起こる条件 下で再集合したヒト膵臓細胞を含む、薬学的に許容しうる担体中の移植組成物。 28.インスリン遺伝子促進制御剤がポリ(ADP−リボース)合成酵素阻害剤 を含む、請求の範囲27の組成物。 29.容器中にHGF/SFの存在下で予め増加させられた低温保存された膵臓 細胞を含む、ヒト膵臓細胞を必要とする患者にヒト膵臓細胞を移植するための材 料を含有する、市販用のキット。 30.容器中にHGF/SFをさらに含む、請求の範囲29のキット。 31.細胞外マトリックスを含有する容器をさらに含む、請求の範囲30のキッ ト。 32.ポリ(ADP−リボース)合成酵素阻害剤を含有する容器をさらに含む、 請求の範囲31のキット。
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US08/235,394 | 1994-04-29 | ||
US08/235,394 US5587309A (en) | 1994-04-29 | 1994-04-29 | Method of stimulating proliferation and differentiation of human fetal pancreatic cells ex vivo |
PCT/US1995/005521 WO1995029989A1 (en) | 1994-04-29 | 1995-04-28 | COMPOSITIONS AND METHOD OF STIMULATING THE PROLIFERATION AND DIFFERENTIATION OF HUMAN FETAL AND ADULT PANCREATIC CELLS $i(EX VIVO) |
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JPH10503923A true JPH10503923A (ja) | 1998-04-14 |
JP3996950B2 JP3996950B2 (ja) | 2007-10-24 |
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US (2) | US5587309A (ja) |
EP (1) | EP0765385B1 (ja) |
JP (1) | JP3996950B2 (ja) |
AT (1) | ATE270323T1 (ja) |
AU (1) | AU695390B2 (ja) |
CA (1) | CA2189052A1 (ja) |
DE (1) | DE69533223T2 (ja) |
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- 1994-04-29 US US08/235,394 patent/US5587309A/en not_active Expired - Lifetime
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- 1995-04-28 WO PCT/US1995/005521 patent/WO1995029989A1/en active IP Right Grant
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- 1995-04-28 EP EP95918374A patent/EP0765385B1/en not_active Expired - Lifetime
- 1995-04-28 DE DE69533223T patent/DE69533223T2/de not_active Expired - Lifetime
- 1995-04-28 AU AU24336/95A patent/AU695390B2/en not_active Ceased
- 1995-04-28 JP JP52851095A patent/JP3996950B2/ja not_active Expired - Fee Related
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AU695390B2 (en) | 1998-08-13 |
DE69533223D1 (de) | 2004-08-05 |
AU2433695A (en) | 1995-11-29 |
JP3996950B2 (ja) | 2007-10-24 |
US5888705A (en) | 1999-03-30 |
EP0765385B1 (en) | 2004-06-30 |
DE69533223T2 (de) | 2005-07-14 |
ATE270323T1 (de) | 2004-07-15 |
WO1995029989A1 (en) | 1995-11-09 |
US5587309A (en) | 1996-12-24 |
CA2189052A1 (en) | 1995-11-09 |
EP0765385A1 (en) | 1997-04-02 |
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