CA2959117C - Methods and compositions for producing hepatocyte-like cells - Google Patents
Methods and compositions for producing hepatocyte-like cells Download PDFInfo
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- CA2959117C CA2959117C CA2959117A CA2959117A CA2959117C CA 2959117 C CA2959117 C CA 2959117C CA 2959117 A CA2959117 A CA 2959117A CA 2959117 A CA2959117 A CA 2959117A CA 2959117 C CA2959117 C CA 2959117C
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| EP3691738A4 (en) * | 2017-10-05 | 2021-06-16 | The Johns Hopkins University | IMPLANTABLE BIOREACTOR AND METHOD FOR MANUFACTURING AND USING THEREOF |
| CN109749981B (zh) * | 2017-11-06 | 2023-10-10 | 博品(上海)生物医药科技有限公司 | 人源脂肪干细胞来源的肝细胞样细胞及其制备方法和应用 |
| CA3112846A1 (en) * | 2018-09-20 | 2020-03-26 | Novadip Biosciences | Biomaterial comprising adipose-derived stem cells and gelatin and method for producing the same |
| BR112022018092A2 (pt) | 2020-03-11 | 2022-11-22 | Bit Bio Ltd | Método de gerar células hepáticas |
| WO2023060186A1 (en) | 2021-10-07 | 2023-04-13 | Hepatx Corporation | Methods of tracking donor cells in a recipient |
| US20230174949A1 (en) * | 2021-12-03 | 2023-06-08 | The Regents Of The University Of California | Engineered vascularized organoids |
Family Cites Families (45)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4491632A (en) | 1979-10-22 | 1985-01-01 | The Massachusetts General Hospital | Process for producing antibodies to hepatitis virus and cell lines therefor |
| US4444887A (en) | 1979-12-10 | 1984-04-24 | Sloan-Kettering Institute | Process for making human antibody producing B-lymphocytes |
| DE3167442D1 (en) | 1980-07-07 | 1985-01-10 | Nat Res Dev | Improvements in or relating to cell lines |
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| US5631734A (en) | 1994-02-10 | 1997-05-20 | Affymetrix, Inc. | Method and apparatus for detection of fluorescently labeled materials |
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| ES2291534T3 (es) | 2001-10-02 | 2008-03-01 | Novo Nordisk Health Care Ag | Metodo para la produccion de proteinas recombinantes en celulas eucariotas. |
| US7413897B2 (en) * | 2002-03-15 | 2008-08-19 | University Of North Carolina At Chapel Hill | Primitive and proximal hepatic stem cells |
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| EP1576148B1 (en) | 2002-12-23 | 2012-10-03 | FUJIFILM Manufacturing Europe B.V. | Process for coating cell-culture support |
| US7813977B2 (en) | 2003-09-11 | 2010-10-12 | Bgc Partners, Inc. | Graphical user interface related to non-standard trading of financial instruments |
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| EP1984488B1 (en) | 2006-01-30 | 2017-12-27 | University Of Virginia Patent Foundation | Methods of preparing and characterizing mesenchymal stem cell aggregates and uses thereof |
| SI2019683T2 (sl) | 2006-04-25 | 2022-10-28 | The Regents Of The University Of California | Dajanje rastnih faktorjev za zdravljenje motenj CŽS |
| CA2650594A1 (en) * | 2006-04-25 | 2007-11-08 | Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College | Adipose derived adult stem cells in hepatic regeneration |
| US7989204B2 (en) * | 2006-04-28 | 2011-08-02 | Viacyte, Inc. | Hepatocyte lineage cells |
| EP2021035B1 (en) * | 2006-05-19 | 2020-08-05 | Versitech Limited | Cell-matrix microspheres, methods for preparation and applications |
| US8158108B2 (en) | 2006-06-28 | 2012-04-17 | S.C. Johnson & Son, Inc. | VOC-free compressed gas aerosol compositions |
| WO2008060360A2 (en) | 2006-09-28 | 2008-05-22 | Surmodics, Inc. | Implantable medical device with apertures for delivery of bioactive agents |
| WO2008144028A1 (en) * | 2007-05-14 | 2008-11-27 | The Johns Hopkins University | Methods for in vivo imaging of cells |
| SG183067A1 (en) * | 2007-07-20 | 2012-08-30 | Cellartis Ab | A novel population of hepatocytes derived via definitive endoderm (de-hep) from human blastocysts derived stem cells |
| CA2712496C (en) | 2008-01-18 | 2021-01-12 | Wei-Shou Hu | Stem cell aggregates and methods for making and using |
| EP2257250A2 (en) | 2008-01-29 | 2010-12-08 | Gilbert H. Kliman | Drug delivery devices, kits and methods therefor |
| US20100112031A1 (en) | 2008-10-17 | 2010-05-06 | University Of Virginia Patent Foundation | Compositions And Methods For Regulating Extracellular Matrix Production In Adipose Derived Cells |
| US20100098739A1 (en) | 2008-10-20 | 2010-04-22 | University Of Virginia Patent Foundation | Compositions and methods for modular soft tissue repair |
| US9057051B2 (en) * | 2008-10-31 | 2015-06-16 | Katholieke Universiteit Leuven | Optimized methods for differentiation of cells into cells with hepatocyte progenitor phenotypes, cells produced by the methods, and methods of using the cells |
| US8895300B2 (en) * | 2008-11-04 | 2014-11-25 | Viacyte, Inc. | Scalable primate pluripotent stem cell aggregate suspension culture and differentiation thereof |
| EP3260534A1 (en) | 2008-11-20 | 2017-12-27 | Janssen Biotech, Inc. | Pluripotent stem cell culture on micro-carriers |
| KR101017710B1 (ko) * | 2009-02-05 | 2011-02-25 | 한양대학교 산학협력단 | 세포 스페로이드 형태의 이식용 성체 줄기세포 집합체 및 그 제조방법 |
| WO2010108126A2 (en) | 2009-03-19 | 2010-09-23 | Fate Therapeutics, Inc. | Reprogramming compositions and methods of using the same |
| US9115238B2 (en) | 2009-05-28 | 2015-08-25 | Corning Incorporated | Swellable synthetic microcarriers for culturing cells |
| JP2011013535A (ja) | 2009-07-03 | 2011-01-20 | Olympus Corp | 光調節装置及び光学系 |
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| US9215088B2 (en) | 2011-06-29 | 2015-12-15 | Broadcom Corporation | Identification of application sessions |
| US20130071931A1 (en) * | 2011-08-02 | 2013-03-21 | National Cancer Center | Process for hepatic differentiation from induced hepatic stem cells, and induced hepatic progenitor cells differentiated thereby |
| EP2554176B1 (en) | 2011-08-04 | 2016-07-27 | ETHIANUM Betriebsgesellschaft mbH & Co. KG | Means for liver regeneration |
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