title: Hepatic differentiation of mouse iPS cells and analysis of liver engraftment potential of multistage iPS progeny.
abstract: Hepatocyte transplantation is considered a promising therapy for patients with liver diseases. Induced pluripotent stem cells (iPSCs) are an unlimited source for the generation of functional hepatocytes. While several protocols that direct the differentiation of iPSCs into hepatocyte-like cells have already been reported, the liver engraftment potential of iPSC progeny obtained at each step of hepatic differentiation has not yet been thoroughly investigated. In this study, we present an efficient strategy to differentiate mouse iPSCs into hepatocyte-like cells and evaluate their liver engraftment potential at different time points of the protocol (5, 10, 15, and 20 days of differentiation). iPSCs were differentiated in the presence of cytokines, growth factors, and small molecules to finally generate hepatocyte-like cells. These iPSC-derived hepatocyte-like cells exhibited hepatocyte-associated functions, such as albumin secretion and urea synthesis. When we transplanted iPSC progeny into the spleen, we found that 15- and 20-day iPSC progeny engrafted into the livers and further acquired hepatocyte morphology. In contrast, 5- and 10-day iPSC progeny were also able to engraft but did not generate hepatocyte-like cells in vivo. Our data may aid in improving current protocols geared towards the use of iPSCs as a new source of liver-targeted cell therapies.
authors.affiliation: Gene Therapy and Hepatology Area, FIMA University of Navarra, Pamplona, Spain.
authors.forename: Anangi
authors.initials: A
authors.lastname: Balasiddaiah
authors.forename: Daniel
authors.initials: D
authors.lastname: Moreno
authors.forename: Laura
authors.initials: L
authors.lastname: Guembe
authors.forename: Jesús
authors.initials: J
authors.lastname: Prieto
authors.forename: Rafael
authors.initials: R
authors.lastname: Aldabe
mesh_terms: D000418:Albumins / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D064987:Cell- and Tissue-Based Therapy; D002478:Cells, Cultured; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D017930:Genes, Reporter; D006085:Graft Survival / Q000276:immunology*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000494:pharmacology; D022781:Hepatocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000637:transplantation*; D008099:Liver / Q000276:immunology / Q000293:injuries; D051379:Mice; D008822:Mice, Transgenic; D013154:Spleen; D013724:Teratoma / Q000276:immunology / Q000378:metabolism; D013997:Time Factors; D014508:Urea / Q000378:metabolism
chemical_list: D000418:Albumins; D015415:Biomarkers; C553307:HGF protein, mouse; D016222:Fibroblast Growth Factor 2; D049452:Green Fluorescent Proteins; D017228:Hepatocyte Growth Factor; D014508:Urea; D000469:Alkaline Phosphatase