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

International Journal of Molecular Sciences

Hua-Ming Chang²  Yi-Wen Liao¹  Chih-Hung Chiang³  Yi-Jen Chen⁴  Ying-Hsiu Lai⁴  Yuh-Lih Chang³  Hen-Li Chen¹  Shaw-Yeu Jeng⁵  Jung-Hung Hsieh⁵  Chi-Hsien Peng⁴  Hsin-Yang Li⁴  Yueh Chien⁴  Szu-Yu Chen²  Liang-Kung Chen⁴ 

[1] Institute of Oral Biology, School of Dentistry, National Yang-Ming University, Taipei, Taiwan; E-Mails:;Department of Optics and Photonics, National Central University, Chung-Li, Taiwan; E-Mails:;Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan; E-Mails:;School of Medicine, National Yang-Ming University, Taipei, Taiwan; E-Mails:;Division of Urology, Department of Surgery, Taipei Veterans General Hospital and Su-Ao/Yuan-Shan Branch, Yilan County, Taiwan; E-Mails:

关键词: induced pluripotent stem cell;    c-Myc;    carbon tetrachloride;    hepatic failure;    hepatic encephalopathy;   

DOI  :  10.3390/ijms13033598

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2012 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland.