CN105601728B - 间充质干细胞分化 - Google Patents
间充质干细胞分化 Download PDFInfo
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- CN105601728B CN105601728B CN201610077451.4A CN201610077451A CN105601728B CN 105601728 B CN105601728 B CN 105601728B CN 201610077451 A CN201610077451 A CN 201610077451A CN 105601728 B CN105601728 B CN 105601728B
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| RU2632155C1 (ru) | 2011-11-08 | 2017-10-02 | Электроникс Энд Телекоммьюникейшнз Рисерч Инститьют | Способ и устройство для совместного использования списка кандидатов |
| US9790264B2 (en) | 2012-06-25 | 2017-10-17 | The Brigham And Women's Hospital, Inc. | Compounds and methods for modulating pharmacokinetics |
| DK2864360T3 (en) * | 2012-06-25 | 2017-12-18 | Brigham & Womens Hospital Inc | TARGETED THERAPY |
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| UY35368A (es) * | 2013-03-08 | 2014-10-31 | Irm Llc | Péptidos y composiciones para el tratamiento de daño articular |
| CN116059196A (zh) | 2013-03-15 | 2023-05-05 | 斯克利普斯研究所 | 用于诱导软骨形成的化合物和方法 |
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| CA3016764A1 (en) | 2016-03-03 | 2017-09-08 | Regeneron Pharmaceuticals, Inc. | Methods for treating patients with hyperlipidemia by administering a pcsk9 inhibitor in combination with an angptl3 inhibitor |
| EP3538127A1 (en) * | 2016-11-14 | 2019-09-18 | Novartis AG | Methods and compositions for treatment of cartilage damage and arthritis |
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| EP3891154B1 (en) | 2018-12-06 | 2023-08-16 | Novartis AG | 5-hydroxy-7-oxabicyclo[2.2.1]heptane-2-carboxamide derivatives for inducing chondrogenesis for treating joint damage |
| CN109432128A (zh) * | 2018-12-07 | 2019-03-08 | 卡替（上海）生物技术股份有限公司 | 牙髓间充质干细胞在银屑病治疗中的应用 |
| KR102246582B1 (ko) * | 2019-04-03 | 2021-04-30 | 이화여자대학교 산학협력단 | 올리고펩타이드를 이용한 줄기세포의 연골세포로의 분화 유도 방법 |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002083851A2 (en) * | 2001-04-10 | 2002-10-24 | Genvec, Inc. | Vegf fusion proteins |
| CN1615440A (zh) * | 2001-11-16 | 2005-05-11 | 杰南技术公司 | 含有血管生成素－样蛋白质3angptl3的组合物及其使用方法 |
| CN1761749A (zh) * | 2003-03-10 | 2006-04-19 | 独立行政法人科学技术振兴机构 | 检测间充质干细胞的标记和采用该标记识别间充质干细胞的方法 |
| CN101001643A (zh) * | 2004-06-21 | 2007-07-18 | 克里夫兰诊所基金会 | 用于干细胞归巢的ccr配体 |
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| US5972338A (en) * | 1997-09-19 | 1999-10-26 | Genentech, Inc. | Tie ligands homologues |
| WO1999055869A1 (en) | 1998-04-27 | 1999-11-04 | Zymogenetics, Inc. | Novel polypeptide growth factors and materials and methods for making them |
| CA2332109A1 (en) | 1998-05-12 | 1999-11-18 | Human Genome Sciences, Inc. | 97 human secreted proteins |
| AU4643699A (en) * | 1998-06-24 | 2000-01-10 | Compugen Ltd. | Angiopoietin-like growth factor sequences |
| KR100553300B1 (ko) | 1999-03-08 | 2006-02-20 | 제넨테크, 인크. | 혈관신생 및 심혈관형성의 촉진 또는 억제 방법 |
| JP2003505350A (ja) | 1999-07-20 | 2003-02-12 | ジェネンテック・インコーポレーテッド | 免疫関連疾患の治療のための組成物と方法 |
| US20030013649A1 (en) * | 2000-01-31 | 2003-01-16 | Rosen Craig A. | Nucleic acids, proteins, and antibodies |
| US20030144498A1 (en) * | 2000-10-16 | 2003-07-31 | Audrey Goddard | TIE ligand homologues |
| US7687460B2 (en) | 2000-10-16 | 2010-03-30 | Genentech, Inc, | Methods of treatment using wisp polypeptides |
| US20030194798A1 (en) * | 2001-05-24 | 2003-10-16 | Surber Mark W. | Minicell compositions and methods |
| PL375883A1 (en) * | 2002-09-09 | 2005-12-12 | Nektar Therapeutics Al, Corporation | Water-soluble polymer alkanals |
| JP3979372B2 (ja) | 2003-09-26 | 2007-09-19 | ブラザー工業株式会社 | 画像処理装置、画像処理方法及び画像処理プログラム |
| AU2006223579A1 (en) | 2005-03-11 | 2006-09-21 | Genentech, Inc. | Gene disruptions, compositions and methods relating thereto |
| JP5139271B2 (ja) | 2005-05-24 | 2013-02-06 | ホワイトヘッド インスティチュート フォー バイオメディカル リサーチ | 培養した造血幹細胞を拡大しかつ分析する方法 |
| US7601501B2 (en) * | 2006-08-11 | 2009-10-13 | The Scripps Research Institute | Controlling osteogenesis by inhibition of osteogenic suppressors |
| WO2008137641A2 (en) | 2007-05-04 | 2008-11-13 | Whitehead Institute For Biomedical Research | Ex vivo expansion of human hematopoietic stem cells |
| US20090104210A1 (en) | 2007-10-17 | 2009-04-23 | Tota Michael R | Peptide compounds for treating obesity and insulin resistance |
| NZ597306A (en) * | 2009-07-14 | 2014-03-28 | Scripps Research Inst | Mesenchymal stem cell differentiation |
| MA38369B1 (fr) | 2013-03-08 | 2018-10-31 | Novartis Ag | Peptides et compositions pour le traitement d'une lesion de l'articulation |
| UY35368A (es) | 2013-03-08 | 2014-10-31 | Irm Llc | Péptidos y composiciones para el tratamiento de daño articular |
-
2010
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002083851A2 (en) * | 2001-04-10 | 2002-10-24 | Genvec, Inc. | Vegf fusion proteins |
| CN1615440A (zh) * | 2001-11-16 | 2005-05-11 | 杰南技术公司 | 含有血管生成素－样蛋白质3angptl3的组合物及其使用方法 |
| CN1761749A (zh) * | 2003-03-10 | 2006-04-19 | 独立行政法人科学技术振兴机构 | 检测间充质干细胞的标记和采用该标记识别间充质干细胞的方法 |
| CN101001643A (zh) * | 2004-06-21 | 2007-07-18 | 克里夫兰诊所基金会 | 用于干细胞归巢的ccr配体 |
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