Converting Skin Fibroblasts into Hepatic-like Cells by Transient Programming
Converting Skin Fibroblasts into Hepatic-like Cells by Transient Programming
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通过瞬时编程将皮肤成纤维细胞转化为肝样细胞
DOI：
10.1002/jcb.25355
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发表时间：
2016
影响因子：
4
通讯作者：
Hu Ji-Fan
中科院分区：
文献类型：
--
作者：
Zhu Xiang-Qing;Pan Xing-Hua;Yao Ling;Li Wei;Cui Jiuwei;Wang Guanjun;Mrsny R;all J.;Hoffman Andrew R.;Hu Ji-Fan
肝细胞移植是终末期肝病的一种有前途的治疗方法，但功能细胞的可用性目前阻碍了其临床应用。我们现在报告了一种简单的瞬时重编程方法，将成纤维细胞转化为肝样细胞。用鱼卵提取物处理人皮肤成纤维细胞，使其成为瞬时重塑细胞（TRC）。感染逆转录病毒EGFP后，直接注射到胎猴肝脏中，在肝脏龛中进行原位分化。肝样细胞具有功能，如体内肝标志物（包括白蛋白、细胞角蛋白-18和肝血清抗原）合成所示。类似地，当植入小鼠肝脏时，TRC分化为合成白蛋白和CK 18的肝样细胞，并完全整合到肝实质中。TRC的效力在机制上与几种信号通路的激活相关，这些信号通路重新激活与细胞效力相关的内源性基因。这项研究证明了一种简单而廉价的表观遗传重塑方法将人成纤维细胞转化为治疗性肝样细胞用于治疗终末期肝病的可行性。J.细胞。117：589-598，2016.© 2015 Wiley Periodicals，Inc.
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.