Therapeutic Potential of HGF-Expressing Human Umbilical Cord Mesenchymal Stem Cells in Mice with Acute Liver Failure.

Yunxia Tang,Fanwei Meng,Xin Zhou,Xingyu Huang,Yixin He,Qiongshu Li,Ji-Fan Hu,Chan Li,Tao Li,Xiaoping Zeng,Xiang Hu,Jia Liu

doi:10.1155/2016/5452487

Abstract

Human umbilical cord-derived mesenchymal stem cells (UCMSCs) are particularly attractive cells for cellular and gene therapy in acute liver failure (ALF). However, the efficacy of this cell therapy in animal studies needs to be significantly improved before it can be translated into clinics. In this study, we investigated the therapeutic potential of UCMSCs that overexpress hepatocyte growth factor (HGF) in an acetaminophen-induced acute liver failure mouse model. We found that the HGF-UCMSC cell therapy protected animals from acute liver failure by reducing liver damage and prolonging animal survival. The therapeutic effect of HGF-UCMSCs was associated with the increment in serum glutathione (GSH) and hepatic enzymes that maintain redox homeostasis, including γ-glutamylcysteine synthetase (γ-GCS), superoxide dismutase (SOD), and catalase (CAT). Immunohistochemical staining confirmed that HGF-UCMSCs were mobilized to the injured areas of the liver. Additionally, HGF-UCMSCs modulated apoptosis by upregulating the antiapoptotic Bcl2 and downregulating proapoptotic genes, including Bax and TNFα. Taken together, these data suggest that ectopic expression of HGF in UCMSCs protects animals from acetaminophen-induced acute liver failure through antiapoptosis and antioxidation mechanisms.

Highlights

Acute liver failure (ALF), a severe liver damage caused by a variety of factors, is characterized by serious liver dysfunction of synthesis, detoxification, excretion, and biotransformation
umbilical cord-derived mesenchymal stem cells (UCMSCs) were cultured from human umbilical cord tissues [20]
We for the first time prove the therapeutic potential of the hepatocyte growth factor (HGF)-expressing UCMSCs in mice with ALF

Summary

Introduction

Acute liver failure (ALF), a severe liver damage caused by a variety of factors, is characterized by serious liver dysfunction of synthesis, detoxification, excretion, and biotransformation. Cell-based therapies have focused on the use of mesenchymal stem cells (MSC) for liver regeneration [6], including those MSCs from human bone marrow [7, 8], umbilical cord blood [9], fetal liver [10, 11], or adipose tissue [1, 12,13,14] These MSC recipes have been approved to induce host liver recovery and stimulate endogenous regeneration programs [2, 3, 12, 14, 15]. The efficacy of these MSC therapies in animal studies still needs to be significantly improved before they can be translated into clinics

Methods

Results

Conclusion