title: Investigation of hepatoprotective activity of induced pluripotent stem cells in the mouse model of liver injury.
abstract: To date liver transplantation is the only effective treatment for end-stage liver diseases. Considering the potential of pluripotency and differentiation into tridermal lineages, induced pluripotent stem cells (iPSCs) may serve as an alternative of cell-based therapy. Herein, we investigated the effect of iPSC transplantation on thioacetamide- (TAA-) induced acute/fulminant hepatic failure (AHF) in mice. Firstly, we demonstrated that iPSCs had the capacity to differentiate into hepatocyte-like cells (iPSC-Heps) that expressed various hepatic markers, including albumin, α-fetoprotein, and hepatocyte nuclear factor-3β, and exhibited biological functions. Intravenous transplantation of iPSCs effectively reduced the hepatic necrotic area, improved liver functions and motor activity, and rescued TAA-treated mice from lethal AHF. 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate cell labeling revealed that iPSCs potentially mobilized to the damaged liver area. Taken together, iPSCs can effectively rescue experimental AHF and represent a potentially favorable cell source of cell-based therapy.
authors.affiliation: Institute of Pharmacology, National Yang-Ming University, No. 155 Section 2 Linong Street, Taipei, Taiwan.
authors.forename: Chih-Hung
authors.initials: CH
authors.lastname: Chiang
authors.forename: Ching-Chih
authors.initials: CC
authors.lastname: Chang
authors.forename: Hui-Chun
authors.initials: HC
authors.lastname: Huang
authors.forename: Yi-Jen
authors.initials: YJ
authors.lastname: Chen
authors.forename: Ping-Hsing
authors.initials: PH
authors.lastname: Tsai
authors.forename: Shaw-Yeu
authors.initials: SY
authors.lastname: Jeng
authors.forename: Shuen-Iu
authors.initials: SI
authors.lastname: Hung
authors.forename: Jung-Hung
authors.initials: JH
authors.lastname: Hsieh
authors.forename: Hsu-Shan
authors.initials: HS
authors.lastname: Huang
authors.forename: Shih-Hwa
authors.initials: SH
authors.lastname: Chiou
authors.forename: Fa-Yauh
authors.initials: FY
authors.lastname: Lee
authors.forename: Shou-Dong
authors.initials: SD
authors.lastname: Lee
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism* / Q000637:transplantation; D007150:Immunohistochemistry; D017114:Liver Failure, Acute / Q000139:chemically induced / Q000473:pathology / Q000628:therapy*; D008111:Liver Function Tests; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008856:Microscopy, Fluorescence; D009336:Necrosis; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism* / Q000637:transplantation*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013853:Thioacetamide
chemical_list: D015415:Biomarkers; D013853:Thioacetamide