title: Animal models to test hiPS-derived hepatocytes in the context of inherited metabolic liver diseases.
abstract: Human induced pluripotent stem (hiPS) cells are established following reprogramming of somatic cells from a wide variety of tissues. Given the scarcity of adult human hepatocytes, hiPS-derived hepatocytes would be a valuable source of cells to study differentiation programs, model patient-specific diseases, test drug toxicities, and cell transplantation therapies. Although hiPS-derived hepatocytes are extensively characterized in cell culture assays, testing these cells in animal models is necessary to fully evaluate their differentiation profile and their lack of tumorigenicity. Immunodeficient mouse models harboring liver damage are effective hosts in which xenogeneic hepatocytes can engraft, proliferate, and participate in liver regeneration, thus constituting a stringent test of hepatocyte functionality. The in vivo evaluation of disease-specific hiPS-derived hepatocytes should broaden our understanding of the cellular and molecular processes involved in inherited metabolic liver disease phenotypes. Herein, we detail our methods to test the functions of hiPS-derived hepatocytes in the context of the immunodeficient Rag2(-/-)IL2Rγc(-/-)Alb-uPAtg mouse model.
authors.affiliation: Innate Immunity Unit, Institut Pasteur, Inserm U668, 25 rue du Docteur Roux, 75724, Paris, France.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Dusséaux
authors.forename: Sylvie
authors.initials: S
authors.lastname: Darche
authors.forename: Helene
authors.initials: H
authors.lastname: Strick-Marchand
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D064987:Cell- and Tissue-Based Therapy; D004195:Disease Models, Animal; D022781:Hepatocytes / Q000166:cytology* / Q000637:transplantation*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D008107:Liver Diseases / Q000628:therapy*; D008115:Liver Regeneration; D008661:Metabolism, Inborn Errors / Q000628:therapy*; D051379:Mice; D018345:Mice, Knockout