BRPI0909866B1 - Método de produção de um meio condicionado de células progenitoras de fígado, meio condicionado e composição farmacêutica - Google Patents
Método de produção de um meio condicionado de células progenitoras de fígado, meio condicionado e composição farmacêutica Download PDFInfo
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| BRPI0909866A2 BRPI0909866A2 (pt) | 2015-08-11 |
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| EP2333047A1 (en) * | 2009-12-09 | 2011-06-15 | Fresenius Medical Care Deutschland GmbH | Adult stem cell derived conditioned medium and/or adult stem cells for use in the therapeutic treatment of a tumor disease |
| US8603470B1 (en) * | 2012-08-07 | 2013-12-10 | National Cheng Kung University | Use of IL-20 antagonists for treating liver diseases |
| DK3016665T3 (da) | 2013-07-05 | 2019-11-25 | Univ Catholique Louvain | Konditioneret medium fra humane voksne leverstamceller og dets anvendelse i behandlingen af leverlidelser |
| BR112016004911A2 (pt) | 2013-09-05 | 2017-09-05 | Inis Biotech Llc | Proteína secretada, acídica e rica em cisteína, um novo alvo para o tratamento e prevenção de insuficiência aguda do fígado |
| RU2644650C2 (ru) * | 2014-12-01 | 2018-02-13 | Общество с ограниченной ответственностью "Т-Хелпер Клеточные Технологии" | Материал стволовых клеток и способ его получения |
| CN104818245B (zh) * | 2015-05-29 | 2020-02-04 | 广州赛莱拉干细胞科技股份有限公司 | 一种肝脏干细胞的培养基及培养方法 |
| AU2017217688B2 (en) | 2016-02-10 | 2023-01-19 | Wake Forest University Health Sciences | Model system of liver fibrosis and method of making and using the same |
| RU2708329C2 (ru) | 2016-05-31 | 2019-12-05 | Общество с ограниченной ответственностью "Т-Хелпер Клеточные Технологии" | Материал стволовых клеток, композиции и способы применения |
| US20200087390A1 (en) | 2016-12-21 | 2020-03-19 | Amgen Inc. | Anti-tnf alpha antibody formulations |
| EP3801028A4 (en) | 2018-05-30 | 2022-04-13 | Direct Biologics LLC | A growth factor and extracellular vesicle frozen or powdered additive comprising a mesenchymal stem cell (msc) preparation and methods of use |
| CN109628377A (zh) * | 2019-01-02 | 2019-04-16 | 贵州省人民医院 | 一种小鼠原代肝细胞灌注式分离及离体培养方法 |
| CN111607556B (zh) | 2019-01-25 | 2022-06-07 | 中国科学院广州生物医药与健康研究院 | 一种培养扩增人肝祖细胞的培养基及其应用 |
| EP3920946A4 (en) | 2019-02-07 | 2022-11-09 | Direct Biologics LLC | METHOD FOR TREATING OSTEOARTHRITIS USING A COMBINATION OF EXOSOMES OF MESENCHYMATE STEM CELLS, SYNOVIAL MESENCHYMATE STEM CELLS AND SCAFFOLDS |
| CN113939585A (zh) * | 2019-04-30 | 2022-01-14 | 普罗米瑟拉疗法公司 | 人同种异体肝源性祖细胞的制备 |
| CN111394391B (zh) * | 2019-07-11 | 2022-12-06 | 上海赛立维生物科技有限公司 | 肝祖细胞样细胞库的构建方法及其制备的细胞株与应用 |
| CA3146433A1 (en) | 2019-07-18 | 2021-01-21 | Direct Biologics Llc | Preparations comprising mesenchymal stem cells and cannabinoids and methods of their use |
| KR20230004709A (ko) | 2020-04-22 | 2023-01-06 | 다이렉트 바이오로직스 엘엘씨 | 감염성 질환과 연관된 염증성 병태를 치료하기 위한 방법 및 조성물 |
| WO2025226276A1 (en) | 2024-04-25 | 2025-10-30 | Direct Biologics, Llc | Treatment of fistula with bone marrow mesenchymal stem cell derived extracellular vesicles |
Family Cites Families (13)
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| JPH093099A (ja) * | 1995-06-20 | 1997-01-07 | Toyobo Co Ltd | マクロファージ刺激蛋白質改変体およびその製造法 |
| US6475490B1 (en) * | 1998-10-19 | 2002-11-05 | Fordham University | Compositions and methods for promoting tissue repair using heat shock proteins |
| US6372494B1 (en) * | 1999-05-14 | 2002-04-16 | Advanced Tissue Sciences, Inc. | Methods of making conditioned cell culture medium compositions |
| US6719969B1 (en) * | 1999-08-09 | 2004-04-13 | The Regents Of The University Of Michigan | Treatment of liver disease and injury with CXC chemokines |
| CA2290240C (en) * | 1999-11-24 | 2008-03-11 | Stergios Stergiopoulos | High resolution 3d ultrasound imaging system deploying a multi-dimensional array of sensors and method for multi-dimensional beamforming sensor signals |
| US7547674B2 (en) * | 2001-06-06 | 2009-06-16 | New York Medical College | Methods and compositions for the repair and/or regeneration of damaged myocardium |
| US6916770B2 (en) | 2001-04-27 | 2005-07-12 | Polyone Corporation | Multi-functional color concentrate compositions |
| CA2452865A1 (en) * | 2001-06-07 | 2002-12-12 | Skinmedica, Inc. | Conditioned cell culture media and uses thereof |
| WO2003033697A1 (en) * | 2001-10-18 | 2003-04-24 | Ixion Biotechnology, Inc. | Conversion of liver stem and progenitor cells to pancreatic functional cells |
| WO2006126219A1 (en) | 2005-05-26 | 2006-11-30 | Fresenius Medical Care Deutschland G.M.B.H. | Liver progenitor cells |
| JP2009527475A (ja) * | 2006-02-16 | 2009-07-30 | バーンハム インスティトゥート フォー メディカル リサーチ | ヒト胚性幹細胞又は他の前駆細胞により馴化された培地、及びその使用 |
| CN103893211A (zh) * | 2006-03-07 | 2014-07-02 | 吉塔·什罗夫 | 包含人胚胎干细胞和其衍生物的组合物、其使用方法和制备方法 |
| FR2912916B1 (fr) * | 2007-02-26 | 2009-05-22 | Oreal | Composition cosmetique ou dermatologique comprenant un milieu de culture cellulaire |
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| CN103800895B (zh) | 2016-12-28 |
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| CA2727392A1 (en) | 2009-12-17 |
| DK2296672T3 (en) | 2016-01-04 |
| BRPI0909866A2 (pt) | 2015-08-11 |
| US10357519B2 (en) | 2019-07-23 |
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| ES2556630T3 (es) | 2016-01-19 |
| CA2727392C (en) | 2017-08-22 |
| CN102119031B (zh) | 2014-09-10 |
| US10456425B2 (en) | 2019-10-29 |
| US20110129439A1 (en) | 2011-06-02 |
| HUE028676T2 (en) | 2016-12-28 |
| CN103800895A (zh) | 2014-05-21 |
| PT2296672E (pt) | 2016-01-22 |
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