Identification of small molecules for human hepatocyte expansion and iPS differentiation. Nat Chem Biol 2013 Aug;9(8):514-20
Date
06/04/2013Pubmed ID
23728495Pubmed Central ID
PMC3720805DOI
10.1038/nchembio.1270Scopus ID
2-s2.0-84880916761 (requires institutional sign-in at Scopus site) 228 CitationsAbstract
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.
Author List
Shan J, Schwartz RE, Ross NT, Logan DJ, Thomas D, Duncan SA, North TE, Goessling W, Carpenter AE, Bhatia SNMESH terms used to index this publication - Major topics in bold
Cell DifferentiationCell Proliferation
Dose-Response Relationship, Drug
Hepatocytes
High-Throughput Screening Assays
Humans
Induced Pluripotent Stem Cells
Molecular Structure
Small Molecule Libraries
Structure-Activity Relationship
