Effects of hepatocyte growth factor gene-transfected mesenchymal stem cells on dimethylnitrosamine-induced liver fibrosis in rats

Growth Factors. 2019 Aug;37(3-4):105-119. doi: 10.1080/08977194.2019.1652399. Epub 2019 Aug 27.

Abstract

Nowadays, transplantation of human mesenchymal stem cells (MSCs) has emerged as a potential cellular therapy for liver cirrhosis. Hepatocyte growth factor (HGF) plays an important role in the regeneration of the liver. The objective of the study was to investigate the therapeutic effect of HGF-transfected human umbilical cord blood-derived MSCs on dimethylnitrosamine (DMN)-induced liver fibrosis in rats. HGF-transfected MSCs were transplanted into rats with DMN-induced liver fibrosis. H2O2-induced cytotoxicity, apoptosis and intracellular reactive oxygen species were reduced in HGF-transfected MSCs in HGF-transfected MSCs. Pro-apoptotic proteins, such as cleaved poly (ADP-ribose) polymerase and cleaved caspase-3, were decreased in HGF-transfected MSCs. Biochemical analysis showed that the levels of aspartate aminotransferase and alanine aminotransferase were decreased after transplantation of HGF-transfected MSCs in rat fibrosis. Trichrome staining showed that HGF-transfected MSCs reduced liver damage. Taken together, our study indicated that HGF-transfected MSCs have therapeutic effects on DMN-induced liver fibrosis in rats.

Keywords: Mesenchymal stem cells (MSCs); hepatocyte growth factor (HGF); liver cirrhosis; stem cell therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine Transaminase / metabolism
  • Animals
  • Apoptosis / physiology
  • Aspartate Aminotransferases / metabolism
  • Caspase 3 / metabolism
  • Cell- and Tissue-Based Therapy / methods*
  • Cells, Cultured
  • Dimethylnitrosamine / toxicity
  • Fetal Blood / cytology
  • Hepatocyte Growth Factor / genetics*
  • Hepatocyte Growth Factor / metabolism*
  • Humans
  • Hydrogen Peroxide / metabolism
  • Liver Cirrhosis / chemically induced
  • Liver Cirrhosis / pathology*
  • Male
  • Mesenchymal Stem Cell Transplantation / methods*
  • Mesenchymal Stem Cells / metabolism
  • Poly(ADP-ribose) Polymerases / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Transfection

Substances

  • Hepatocyte Growth Factor
  • Hydrogen Peroxide
  • Poly(ADP-ribose) Polymerases
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Caspase 3
  • Dimethylnitrosamine