Directed differentiation of induced pluripotent stem cells to hepatic stellate cells

In healthy liver, quiescent hepatic stellate cells (HSCs) participate in the homeostasis of extracellular matrix and store vitamin A. After injury, HSCs activate and participate in the wound-healing response, producing extracellular matrix components and eventually fibrosis.  We have developed a protocol to direct the differentiation of human induced pluripotent stem cells (iPSC) to HSCs. The final HSC–like population was enriched in PDGFRß positive cells and expressed key HSC markers at similar levels than primary HSC. Whole genome transcriptomic analysis revealed that PSC-derived population displayed an intermediate phenotype between activated and quiescent HSCs. Functional analysis showed that PSC-derived HSC-like cells responded to injury mediators and accumulated retinyl esters into lipid droplets. These findings show that we have generated functional HSC-like cells from iPSC, which may have potential for in vitro and biomedical applications