Identification of small molecules for human hepatocyte expansion and iPS differentiation

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.