Identification of small molecules for human hepatocyte expansion and iPS differentiation

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Author
Shan, Jing
Ross, Nathan T.
Logan, David J.
Thomas, David
Duncan, Stephen A.
Carpenter, Anne E.
Published Version
https://doi.org/10.1038/nchembio.1270Metadata
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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. 2013. “Identification of small molecules for human hepatocyte expansion and iPS differentiation.” Nature chemical biology 9 (8): 514-520. doi:10.1038/nchembio.1270. http://dx.doi.org/10.1038/nchembio.1270.Abstract
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 been limiting 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. One class induced functional proliferation of primary human hepatocytes in vitro. The second class enhanced hepatocyte functions and promoted differentiation of iPS-derived hepatocytes, toward a phenotype more mature than what was previously obtainable. The identification of these small molecules can help to address a major challenge impacting many facets of liver research and may lead to the development of novel therapeutics for liver diseases.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3720805/pdf/Terms of Use
This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAACitable link to this page
http://nrs.harvard.edu/urn-3:HUL.InstRepos:11879936
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