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 fibrob...

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Bibliographic Details
Published in:Journal of cellular biochemistry 2016-03, Vol.117 (3), p.589-598
Main Authors: Zhu, Xiang-Qing, Pan, Xing-Hua, Yao, Ling, Li, Wei, Cui, Jiuwei, Wang, Guanjun, Mrsny, Randall J., Hoffman, Andrew R., Hu, Ji-Fan
Format: Article
Language:English
Subjects:
Animals
Cells, Cultured
Cellular Reprogramming
DIFFERENTIATION
EPIGENETICS
Female
Fibroblasts - physiology
Fibroblasts - transplantation
FISH OOCYTE EXTRACTS
HEPATOCYTE-LIKE CELLS
Hepatocytes - metabolism
Humans
Keratin-18 - metabolism
Liver - cytology
Liver Regeneration
Macaca mulatta
Male
Mice, Inbred BALB C
Pluripotent Stem Cells - metabolism
Pluripotent Stem Cells - transplantation
Signal Transduction
Skin - cytology
STEM CELL
TRANSIENT REPROGRAMMING
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Summary: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. J. Cell. Biochem. 117: 589–598, 2016. © 2015 Wiley Periodicals, Inc.
ISSN:0730-2312
1097-4644
DOI:10.1002/jcb.25355