Year 4

The objective of this project is to establish the feasibility of liver cell therapy with human induced hepatocyte-like cells (iHeps). As proposed we established the feasibility of generating iHeps from several expandable, potentially autologous human cell types, using nonintegrating (episomal) vectors. For this, we identified transcription factors effective in inducing hepatocyte differentiation of these cells. We also identified small molecules and culture conditions (extracellular matrix composition and stiffness) that promote proliferation and hepatocyte-specific differentiation. Finally, we established the therapeutic efficacy and principal safety of these cells.