AUG 30, 2016 08:00 AM PDT

Directed differentiation of induced pluripotent stem cells to hepatic stellate cells

  • IDIBAPS Researcher, Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Spain
      Pau Sancho-Bru received his PhD in 2006 from the University of Barcelona. In 2007 he joined the Stem Cell Institute Leuven at the KU Leuven, Belgium as a postdoctoral researcher. In 2012 he was appointed Researcher in IDIBAPS. Pau Sancho-Bru is Principal Investigator at the Liver Injury and Repair Group and Researcher at IDIBAPS. His group is focused on understanding the mechanisms governing liver injury and regeneration and particularly the role of hepatic stellate cells and liver stem/progenitor cells in wound-healing responses. One of the main research interests of his group is developing in vitro systems for disease modeling and assessing the potential of stem cells for biomedical and biotechnological applications.

    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

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