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

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

Disclosure statement

The authors declare that there are no conflicts of interest.

Additional information

Funding

This work was supported by a grant from the Business for Cooperative R&D between Industry, Academy, and Research Institutes (Grant no. C0443066) funded by the Korean Small and Medium Business Administration in 2016. This work was also supported by the Gachon University Gil Medical Center (Grant no. 2016-14).