Improvement of Carbon Tetrachloride-Induced Acute Hepatic Failure by Transplantation of Induced Pluripotent Stem Cells without Reprogramming Factor c-Myc |
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Authors: | Chang Hua-Ming Liao Yi-Wen Chiang Chih-Hung Chen Yi-Jen Lai Ying-Hsiu Chang Yuh-Lih Chen Hen-Li Jeng Shaw-Yeu Hsieh Jung-Hung Peng Chi-Hsien Li Hsin-Yang Chien Yueh Chen Szu-Yu Chen Liang-Kung Huo Teh-Ia |
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Affiliation: | Department of Optics and Photonics, National Central University, Chung-Li, Taiwan; E-Mails: vdty1009@mail5.vac.gov.tw (H.-M.C.); syc370@ncu.edu.tw (S.-Y.C.). |
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Abstract: | The only curative treatment for hepatic failure is liver transplantation. Unfortunately, this treatment has several major limitations, as for example donor organ shortage. A previous report demonstrated that transplantation of induced pluripotent stem cells without reprogramming factor c-Myc (3-genes iPSCs) attenuates thioacetamide-induced hepatic failure with minimal incidence of tumorigenicity. In this study, we investigated whether 3-genes iPSC transplantation is capable of rescuing carbon tetrachloride (CCl(4))-induced fulminant hepatic failure and hepatic encephalopathy in mice. Firstly, we demonstrated that 3-genes iPSCs possess the capacity to differentiate into hepatocyte-like cells (iPSC-Heps) that exhibit biological functions and express various hepatic specific markers. 3-genes iPSCs also exhibited several antioxidant enzymes that prevented CCl(4)-induced reactive oxygen species production and cell death. Intraperitoneal transplantation of either 3-genes iPSCs or 3-genes iPSC-Heps significantly reduced hepatic necrotic areas, improved hepatic functions, and survival rate in CCl(4)-treated mice. CCl(4)-induced hepatic encephalopathy was also improved by 3-genes iPSC transplantation. Hoechst staining confirmed the successful engraftment of both 3-genes iPSCs and 3-genes iPSC-Heps, indicating the homing properties of these cells. The most pronounced hepatoprotective effect of iPSCs appeared to originate from the highest antioxidant activity of 3-gene iPSCs among all transplanted cells. In summary, our findings demonstrated that 3-genes iPSCs serve as an available cell source for the treatment of an experimental model of acute liver diseases. |
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Keywords: | induced pluripotent stem cell c-Myc carbon tetrachloride hepatic failure hepatic encephalopathy |
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