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Int. J. Mol. Sci. 2012, 13(3), 3598-3617; doi:10.3390/ijms13033598
Article

Improvement of Carbon Tetrachloride-Induced Acute Hepatic Failure by Transplantation of Induced Pluripotent Stem Cells without Reprogramming Factor c-Myc

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1 Department of Optics and Photonics, National Central University, Chung-Li, Taiwan 2 Institute of Oral Biology, School of Dentistry, National Yang-Ming University, Taipei, Taiwan 3 Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan 4 Division of Urology, Department of Surgery, Taipei Veterans General Hospital and Su-Ao/Yuan-Shan Branch, Yilan County, Taiwan 5 School of Medicine, National Yang-Ming University, Taipei, Taiwan 6 Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan 7 Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan 8 Shin Kong Wu Ho-Su Memorial Hospital and Fu-Jen Catholic University, Taipei, Taiwan 9 Center for Geriatrics and Gerontology, Taipei Veterans General Hospital, Taipei, Taiwan 10 Division of Gastroenterology, Department of Internal Medicine, Taipei Veterans General Hospital, Taipei, Taiwan These authors contributed equally to this work.
* Authors to whom correspondence should be addressed.
Received: 16 January 2012 / Revised: 13 February 2012 / Accepted: 28 February 2012 / Published: 16 March 2012
(This article belongs to the Section Bioinorganic Chemistry)
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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 (CCl4)-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 CCl4-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 CCl4-treated mice. CCl4-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.
Keywords: induced pluripotent stem cell; c-Myc; carbon tetrachloride; hepatic failure; hepatic encephalopathy induced pluripotent stem cell; c-Myc; carbon tetrachloride; hepatic failure; hepatic encephalopathy
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Chang, H.-M.; Liao, Y.-W.; Chiang, C.-H.; Chen, Y.-J.; Lai, Y.-H.; Chang, Y.-L.; Chen, H.-L.; Jeng, S.-Y.; Hsieh, J.-H.; Peng, C.-H.; Li, H.-Y.; Chien, Y.; Chen, S.-Y.; Chen, L.-K.; Huo, T.-I. Improvement of Carbon Tetrachloride-Induced Acute Hepatic Failure by Transplantation of Induced Pluripotent Stem Cells without Reprogramming Factor c-Myc. Int. J. Mol. Sci. 2012, 13, 3598-3617.

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Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert