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

Publication Type:

Journal Article

Source:

Nat Chem Biol, Volume 9, Issue 8, p.514-20 (2013)

Keywords:

Cell 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.

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