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PMID: 23728495 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

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

Nature chemical biology ·Vol. 9 ·No. 8 ·2013-08-00 ·Pages 514-20

Shan J, Schwartz RE, Ross NT, Logan DJ, Thomas D, Duncan SA, North TE, Goessling W, Carpenter AE, Bhatia SN

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.

MeSH Terms
Cell Differentiation/drug effects Cell Proliferation Dose-Response Relationship, Drug Hepatocytes/cytology,drug effects High-Throughput Screening Assays Humans Induced Pluripotent Stem Cells/cytology,drug effects Molecular Structure Small Molecule Libraries/chemistry,pharmacology Structure-Activity Relationship
Chemicals
Small Molecule Libraries
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Shan Jing
Harvard-Massachusetts Institute of Technology Division of Health Sciences and Technology, MIT, Cambridge, Massachusetts, USA.
Schwartz Robert E
Ross Nathan T
Logan David J
Thomas David
Duncan Stephen A
North Trista E
Goessling Wolfram
Carpenter Anne E
Bhatia Sangeeta N
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Article Info
Journal
Nature chemical biology
Abbr.
Nat Chem Biol
ISSN
1552-4469
DOI
10.1038/nchembio.1270
Published
2013-08-00
Epub
2013-00-02
Pages
514-20
Language
English
Region
United States
NLM ID
101231976
PMCID
PMC3720805
Subset
IM
Grants
NIDDK NIH HHS · R01-DK56966 · United States
NIDDK NIH HHS · R01 DK055743 · United States
NHLBI NIH HHS · HL094857 · United States
NIDDK NIH HHS · R01 DK098241 · United States
NIDDK NIH HHS · DK087377 · United States
NIDDK NIH HHS · DK55743 · United States
NIDDK NIH HHS · DK085445 · United States
NHGRI NIH HHS · HG006398 · United States
NIDDK NIH HHS · RC1 DK087377 · United States
NHGRI NIH HHS · U01 HG006398 · United States
NIDDK NIH HHS · R01 DK065152 · United States
NIDDK NIH HHS · R03 DK085445 · United States
NIDDK NIH HHS · R01 DK056966 · United States
NCI NIH HHS · P30 CA014051 · United States
NIGMS NIH HHS · R01 GM0896 · United States
NIDDK NIH HHS · R01 DK085713 · United States
NIGMS NIH HHS · R01 GM089652 · United States
Howard Hughes Medical Institute · United States
NIDDK NIH HHS · R01 DK090311 · United States
NHLBI NIH HHS · R01 HL094857 · United States
NIDDK NIH HHS · R01-DK065152 · United States
Databases
PubChem-Substance
162210945, 162210946, 162210947, 162210948, 162210949, 162210950, 162210951, 162210952, 162210953, 162210954
External Links
PubMed source DOI: 10.1038/nchembio.1270 PMC Full Text View journal details
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