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Converting Skin Fibroblasts into Hepatic‐like Cells by Transient Programming
Author(s) -
Zhu XiangQing,
Pan XingHua,
Yao Ling,
Li Wei,
Cui Jiuwei,
Wang Guanjun,
Mrsny Randall J.,
Hoffman Andrew R.,
Hu JiFan
Publication year - 2016
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.25355
Subject(s) - transient (computer programming) , microbiology and biotechnology , chemistry , computer science , biology , programming language
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. J. Cell. Biochem. 117: 589–598, 2016. © 2015 Wiley Periodicals, Inc.