Improvement of carbon tetrachloride-induced acute hepatic failure by transplantation of induced pluripotent stem cells without reprogramming factor c-Myc

Hua Ming Chang, Yi Wen Liao, Chih Hung Chiang, Yi Jen Chen, Ying Hsiu Lai, Yuh Lih Chang, Hen Li Chen, Shaw Yeu Jeng, Jung Hung Hsieh, Chi Hsien Peng, Hsin Yang Li, Yueh Chien, Szu Yu Chen, Liang Kung Chen, Teh Ia Huo

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

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.

Original languageEnglish
Pages (from-to)3598-3617
Number of pages20
JournalInternational Journal of Molecular Sciences
Volume13
Issue number3
DOIs
StatePublished - Mar 2012

Keywords

  • C-Myc
  • Carbon tetrachloride
  • Hepatic encephalopathy
  • Hepatic failure
  • Induced pluripotent stem cell

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