TW201636421A - 多潛能幹細胞之懸浮培養 - Google Patents
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Families Citing this family (18)
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| EP3408375A4 (en) | 2016-01-26 | 2019-07-17 | Centre for Commercialization of Regenerative Medicine | PROCESS FOR DISSOCIATION OF CELL AGGREGATES |
| US10391156B2 (en) | 2017-07-12 | 2019-08-27 | Viacyte, Inc. | University donor cells and related methods |
| JP2020527956A (ja) * | 2017-07-21 | 2020-09-17 | センマ・セラピューティクス・インコーポレーテッド | 幹細胞由来の膵臓ベータ細胞の再凝集 |
| US20200199540A1 (en) * | 2017-09-11 | 2020-06-25 | Novo Nordisk A/S | Enrichment of nkx6.1 and c-peptide co-expressing cells derived in vitro from stem cells |
| CN118497104A (zh) | 2017-11-15 | 2024-08-16 | 沃泰克斯药物股份有限公司 | 胰岛细胞制备性组合物和使用方法 |
| EP3833365A4 (en) | 2018-08-10 | 2022-05-11 | Vertex Pharmaceuticals Incorporated | Stem cell derived islet differentiation |
| US10724052B2 (en) | 2018-09-07 | 2020-07-28 | Crispr Therapeutics Ag | Universal donor cells |
| TWI862513B (zh) * | 2018-09-19 | 2024-11-21 | 日商千紙鶴治療公司 | 包含胰島素產生細胞之細胞集團、包含該細胞集團之醫藥、其用途及製造方法 |
| CN113728090B (zh) * | 2019-04-08 | 2024-04-05 | 诺和诺德股份有限公司 | 从干细胞衍生的定形内胚层生成胰腺内胚层 |
| JP7555975B2 (ja) | 2019-05-31 | 2024-09-25 | ダブリュ．エル．ゴア アンド アソシエイツ，インコーポレイティド | 生体適合性メンブレン複合体 |
| WO2020243666A1 (en) | 2019-05-31 | 2020-12-03 | W. L. Gore & Associates, Inc. | A biocompatible membrane composite |
| JP2022534545A (ja) | 2019-05-31 | 2022-08-01 | ダブリュ．エル．ゴア アンド アソシエイツ，インコーポレイティド | 生体適合性メンブレン複合体 |
| CA3257300A1 (en) | 2019-05-31 | 2025-06-12 | W. L. Gore & Associates, Inc. | Cell encapsulation devices with controlled oxygen diffusion distances |
| US11118195B2 (en) | 2019-09-05 | 2021-09-14 | Crispr Therapeutics Ag | Universal donor cells |
| AU2020340622A1 (en) | 2019-09-05 | 2022-03-03 | Crispr Therapeutics Ag | Universal donor cells |
| KR20230146007A (ko) | 2020-12-31 | 2023-10-18 | 크리스퍼 테라퓨틱스 아게 | 범용 공여자 세포 |
| CN119432595A (zh) * | 2023-08-07 | 2025-02-14 | 浙江霍德生物工程有限公司 | 利用生物反应器进行诱导多能干细胞的悬浮培养 |
| WO2025117331A1 (en) * | 2023-12-01 | 2025-06-05 | Eli Lilly And Company | Methods of making stem cell-derived islet-like cells, as well as populations and compositions including the same |
Family Cites Families (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5843780A (en) | 1995-01-20 | 1998-12-01 | Wisconsin Alumni Research Foundation | Primate embryonic stem cells |
| CN101240262A (zh) | 2001-12-07 | 2008-08-13 | 杰龙公司 | 源自人胚胎干细胞的胰岛细胞 |
| ES2564044T3 (es) | 2003-06-27 | 2016-03-17 | DePuy Synthes Products, Inc. | Células posparto derivadas de tejido del cordón umbilical y métodos de preparación y uso de las mismas |
| US20050266554A1 (en) * | 2004-04-27 | 2005-12-01 | D Amour Kevin A | PDX1 expressing endoderm |
| JP4819697B2 (ja) | 2003-12-23 | 2011-11-24 | ヴィアサイト，インコーポレイテッド | 胚体内胚葉 |
| KR101178786B1 (ko) | 2004-03-23 | 2012-09-07 | 다이이찌 산쿄 가부시키가이샤 | 다능성 줄기세포의 증식 방법 |
| 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 |
| AU2006202209B2 (en) | 2005-05-27 | 2011-04-14 | Lifescan, Inc. | Amniotic fluid derived cells |
| US8476070B2 (en) | 2005-08-29 | 2013-07-02 | Technion Research & Development Foundation Limited | Media for culturing stem cells |
| EP3584311A1 (en) * | 2005-10-27 | 2019-12-25 | Viacyte, Inc. | Pdx-1 expressing dorsal and ventral foregut endoderm |
| US7695965B2 (en) | 2006-03-02 | 2010-04-13 | Cythera, Inc. | Methods of producing pancreatic hormones |
| DK2650359T3 (da) * | 2006-03-02 | 2022-06-13 | Viacyte Inc | Endokrine prekursorceller, pancreatiske hormon-udtrykkende celler og fremstillingsfremgangsmåder |
| AU2007277364B2 (en) | 2006-07-26 | 2010-08-12 | Viacyte, Inc. | Methods of producing pancreatic hormones |
| ES2704401T3 (es) | 2006-08-02 | 2019-03-18 | Technion Res & Dev Foundation | Métodos de expansión de células madre embrionarias en un cultivo en suspensión |
| DK2173863T3 (en) | 2007-06-29 | 2019-01-21 | Fujifilm Cellular Dynamics Inc | Automated method and apparatus for embryonic stem cell culture |
| KR101651661B1 (ko) * | 2008-06-30 | 2016-08-26 | 얀센 바이오테크 인코포레이티드 | 만능 줄기 세포의 분화 |
| WO2010022395A2 (en) * | 2008-08-22 | 2010-02-25 | President And Fellows Of Harvard College | Methods of reprogramming cells |
| CN102695790A (zh) | 2009-10-29 | 2012-09-26 | 詹森生物科技公司 | 多能干细胞 |
| WO2011139628A1 (en) * | 2010-04-25 | 2011-11-10 | Mount Sinai School Of Medicine | Generation of anterior foregut endoderm from pluripotent cells |
| US9388386B2 (en) * | 2011-12-22 | 2016-07-12 | Janssen Biotech, Inc. | Differentiation of human embryonic stem cells into single hormonal insulin positive cells |
| RU2684215C2 (ru) * | 2012-12-31 | 2019-04-04 | Янссен Байотек, Инк. | Способ получения панкреатических эндокринных клеток (варианты) и способ увеличения выхода бета-клеток |
| 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 |
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| PH12017501153A1 (en) | 2017-11-27 |
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| KR102519502B1 (ko) | 2023-04-06 |
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| AU2015363008B2 (en) | 2021-12-09 |
| ZA201704868B (en) | 2019-02-27 |
| CN107250349A (zh) | 2017-10-13 |
| RU2017125728A3 (enExample) | 2019-06-03 |
| RU2017125728A (ru) | 2019-01-22 |
| JP6800854B2 (ja) | 2020-12-16 |
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