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Nat Chem Biol DOI:10.1038/nchembio.1270

Identification of small molecules for human hepatocyte expansion and iPS differentiation.

Publication TypeJournal Article
Year of Publication2013
AuthorsShan, J, Schwartz, RE, Ross, NT, Logan, DJ, Thomas, D, Duncan, SA, North, TE, Goessling, W, Carpenter, AE, Bhatia, SN
JournalNat Chem Biol
Volume9
Issue8
Pages514-20
Date Published2013 Aug
ISSN1552-4469
KeywordsCell Differentiation, Cell Proliferation, Dose-Response Relationship, Drug, Hepatocytes, High-Throughput Screening Assays, Humans, Induced Pluripotent Stem Cells, Molecular Structure, Small Molecule Libraries, Structure-Activity Relationship
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 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.

URLhttp://dx.doi.org/10.1038/nchembio.1270
DOI10.1038/nchembio.1270
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/23728495?dopt=Abstract

Alternate JournalNat. Chem. Biol.
PubMed ID23728495
PubMed Central IDPMC3720805
Grant ListR01 DK065152 / DK / NIDDK NIH HHS / United States
R03 DK085445 / DK / NIDDK NIH HHS / United States
R01 DK056966 / DK / NIDDK NIH HHS / United States
R01-DK56966 / DK / NIDDK NIH HHS / United States
R01 DK055743 / DK / NIDDK NIH HHS / United States
HL094857 / HL / NHLBI NIH HHS / United States
R01 DK098241 / DK / NIDDK NIH HHS / United States
P30 CA014051 / CA / NCI NIH HHS / United States
R01 GM0896 / GM / NIGMS NIH HHS / United States
R01 DK085713 / DK / NIDDK NIH HHS / United States
DK087377 / DK / NIDDK NIH HHS / United States
DK55743 / DK / NIDDK NIH HHS / United States
P30 ES002109 / ES / NIEHS NIH HHS / United States
R01 GM089652 / GM / NIGMS NIH HHS / United States
/ / Howard Hughes Medical Institute / United States
DK085445 / DK / NIDDK NIH HHS / United States
HG006398 / HG / NHGRI NIH HHS / United States
RC1 DK087377 / DK / NIDDK NIH HHS / United States
R01 DK090311 / DK / NIDDK NIH HHS / United States
R01 HL094857 / HL / NHLBI NIH HHS / United States
R01-DK065152 / DK / NIDDK NIH HHS / United States
U01 HG006398 / HG / NHGRI NIH HHS / United States