Identification of small molecules for human hepatocyte expansion and iPS differentiation
Cell-based therapies hold the potential to alleviate the growing burden of liver diseases. Such therapies require human hepatocytes, which, within the stromal context of the liver, are capable of many rounds of replication. However, this ability is lost ex vivo, and human hepatocyte sourcing has lim...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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2014
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| Online Access: | http://hdl.handle.net/1721.1/86114 https://orcid.org/0000-0003-0590-9937 https://orcid.org/0000-0002-1293-2097 |
| _version_ | 1826197011280429056 |
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| author | Shan, Jing Ross, Nathan T. Logan, David J. Thomas, David Duncan, Stephen A. North, Trista E. Goessling, Wolfram Carpenter, Anne E. Schwartz, Robert E. Bhatia, Sangeeta N |
| author2 | Whitaker College of Health Sciences and Technology |
| author_facet | Whitaker College of Health Sciences and Technology Shan, Jing Ross, Nathan T. Logan, David J. Thomas, David Duncan, Stephen A. North, Trista E. Goessling, Wolfram Carpenter, Anne E. Schwartz, Robert E. Bhatia, Sangeeta N |
| author_sort | Shan, Jing |
| collection | MIT |
| description | Cell-based therapies hold the potential to alleviate the growing burden of liver diseases. Such therapies require human hepatocytes, which, within the stromal context of the liver, are capable of many rounds of replication. However, this ability is lost ex vivo, and human hepatocyte sourcing has limited many fields of research for decades. Here we developed a high-throughput screening platform for primary human hepatocytes to identify small molecules in two different classes that can be used to generate renewable sources of functional human hepatocytes. The first class induced functional proliferation of primary human hepatocytes in vitro. The second class enhanced hepatocyte functions and promoted the differentiation of induced pluripotent stem cell–derived hepatocytes toward a more mature phenotype than what was previously obtainable. The identification of these small molecules can help address a major challenge affecting many facets of liver research and may lead to the development of new therapeutics for liver diseases. |
| first_indexed | 2024-09-23T10:41:20Z |
| format | Article |
| id | mit-1721.1/86114 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T10:41:20Z |
| publishDate | 2014 |
| record_format | dspace |
| spelling | mit-1721.1/861142022-09-27T14:15:11Z Identification of small molecules for human hepatocyte expansion and iPS differentiation Shan, Jing Ross, Nathan T. Logan, David J. Thomas, David Duncan, Stephen A. North, Trista E. Goessling, Wolfram Carpenter, Anne E. Schwartz, Robert E. Bhatia, Sangeeta N Whitaker College of Health Sciences and Technology Massachusetts Institute of Technology. Institute for Medical Engineering & Science Harvard University--MIT Division of Health Sciences and Technology Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science Koch Institute for Integrative Cancer Research at MIT Shan, Jing Schwartz, Robert Bhatia, Sangeeta N. Cell-based therapies hold the potential to alleviate the growing burden of liver diseases. Such therapies require human hepatocytes, which, within the stromal context of the liver, are capable of many rounds of replication. However, this ability is lost ex vivo, and human hepatocyte sourcing has limited many fields of research for decades. Here we developed a high-throughput screening platform for primary human hepatocytes to identify small molecules in two different classes that can be used to generate renewable sources of functional human hepatocytes. The first class induced functional proliferation of primary human hepatocytes in vitro. The second class enhanced hepatocyte functions and promoted the differentiation of induced pluripotent stem cell–derived hepatocytes toward a more mature phenotype than what was previously obtainable. The identification of these small molecules can help address a major challenge affecting many facets of liver research and may lead to the development of new therapeutics for liver diseases. Broad Institute of MIT and Harvard (Scientific Planning and Allocation of Resources Committee Grant) National Institutes of Health (U.S.) (Grant NIH R01-DK065152) National Institutes of Health (U.S.) (Grant NIH R01-DK56966) 2014-04-11T17:04:24Z 2014-04-11T17:04:24Z 2013-06 2012-12 Article http://purl.org/eprint/type/JournalArticle 1552-4450 1552-4469 http://hdl.handle.net/1721.1/86114 Shan, Jing, Robert E Schwartz, Nathan T Ross, David J Logan, David Thomas, Stephen A Duncan, Trista E North, Wolfram Goessling, Anne E Carpenter, and Sangeeta N Bhatia. “Identification of Small Molecules for Human Hepatocyte Expansion and iPS Differentiation.” Nat Chem Biol 9, no. 8 (June 2, 2013): 514–520. https://orcid.org/0000-0003-0590-9937 https://orcid.org/0000-0002-1293-2097 en_US http://dx.doi.org/10.1038/nchembio.1270 Nature Chemical Biology Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf PMC |
| spellingShingle | Shan, Jing Ross, Nathan T. Logan, David J. Thomas, David Duncan, Stephen A. North, Trista E. Goessling, Wolfram Carpenter, Anne E. Schwartz, Robert E. Bhatia, Sangeeta N Identification of small molecules for human hepatocyte expansion and iPS differentiation |
| title | Identification of small molecules for human hepatocyte expansion and iPS differentiation |
| title_full | Identification of small molecules for human hepatocyte expansion and iPS differentiation |
| title_fullStr | Identification of small molecules for human hepatocyte expansion and iPS differentiation |
| title_full_unstemmed | Identification of small molecules for human hepatocyte expansion and iPS differentiation |
| title_short | Identification of small molecules for human hepatocyte expansion and iPS differentiation |
| title_sort | identification of small molecules for human hepatocyte expansion and ips differentiation |
| url | http://hdl.handle.net/1721.1/86114 https://orcid.org/0000-0003-0590-9937 https://orcid.org/0000-0002-1293-2097 |
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