title: Converting Skin Fibroblasts into Hepatic-like Cells by Transient Programming.
abstract: Transplantation of hepatocytes is a promising therapy for end-stage liver disease, but the availability of functional cells currently precludes its clinical application. We now report a simple transient reprogramming approach to convert fibroblasts into hepatic-like cells. Human skin fibroblasts were treated with fish egg extracts to become the transiently remodeled cells (TRCs). After infected with retroviral EGFP, they were directly injected into the fetal monkey liver, where they underwent in situ differentiation in the hepatic niche. The hepatic-like cells were functional as shown by the synthesis of hepatic markers in vivo, including albumin, cytokeratin-18, and hepatic serum antigen. Similarly, when implanted in the mouse liver, the TRCs were differentiated into hepatic-like cells that synthesize albumin and CK18 and became completely integrated into the liver parenchyma. The potency of TRCs was mechanistically related to the activation of several signal pathways, which reactivate endogenous genes related to cell potency. This study demonstrates the feasibility of a simple and inexpensive epigenetic remodeling approach to convert human fibroblasts into therapeutic hepatic-like cells for the treatment of end-stage liver disease.
authors: Research Center of Stem Cell, Tissue and Organ Engineering, Kunming Army General Hospital, Kunming, Yunnan, P. R. China.
authors: Xiang-Qing
authors: XQ
authors: Zhu
authors: Research Center of Stem Cell, Tissue and Organ Engineering, Kunming Army General Hospital, Kunming, Yunnan, P. R. China.
authors: Xing-Hua
authors: XH
authors: Pan
authors: Stanford University Medical School, Palo Alto, California.
authors: Ling
authors: L
authors: Yao
authors: Stem Cell and Cancer Center, The First Affiliated Hospital, Jilin University, Changchun, P. R. China.
authors: Wei
authors: W
authors: Li
authors: Stem Cell and Cancer Center, The First Affiliated Hospital, Jilin University, Changchun, P. R. China.
authors: Jiuwei
authors: J
authors: Cui
authors: Stem Cell and Cancer Center, The First Affiliated Hospital, Jilin University, Changchun, P. R. China.
authors: Guanjun
authors: G
authors: Wang
authors: GMR Epigenetics, Palo Alto, California.|Department of Pharmacy & Pharmacology, University of Bath, Bath, England.
authors: Randall J
authors: RJ
authors: Mrsny
authors: Stanford University Medical School, Palo Alto, California.
authors: Andrew R
authors: AR
authors: Hoffman
authors: Stanford University Medical School, Palo Alto, California.|Stem Cell and Cancer Center, The First Affiliated Hospital, Jilin University, Changchun, P. R. China.
authors: Ji-Fan
authors: JF
authors: Hu
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D065150:Cellular Reprogramming; D005260:Female; D005347:Fibroblasts / Q000502:physiology* / Q000637:transplantation; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D053538:Keratin-18 / Q000378:metabolism; D008099:Liver / Q000166:cytology; D008115:Liver Regeneration; D008253:Macaca mulatta; D008297:Male; D008807:Mice, Inbred BALB C; D039904:Pluripotent Stem Cells / Q000378:metabolism / Q000637:transplantation; D015398:Signal Transduction; D012867:Skin / Q000166:cytology
chemical_list: C488421:KRT18 protein, human; D053538:Keratin-18
keywords: DIFFERENTIATION; EPIGENETICS; FISH OOCYTE EXTRACTS; HEPATOCYTE-LIKE CELLS; STEM CELL; TRANSIENT REPROGRAMMING