Therapeutic effect of hepatocyte growth factor-overexpressing bone marrow-derived mesenchymal stem cells on CCl4-induced hepatocirrhosis.

Abstract

Hepatocirrhosis is one of the most severe complications of chronic hepatic disease in terms of medical intervention, and the available therapies are limited and not very successful. In this study, bone marrow-derived mesenchymal stem cells (BM-MSCs) from host rats were transduced with an adenoviral vector labelled with green fluorescent protein (EGFP) to overexpress hepatocyte growth factor (HGF). The therapeutic effect of these modified stem cells (HGF-BM-MSC group) transplanted intravenously into hepatocirrhosis model rats treated with CCl4 was evaluated using serological, biochemical and histological approaches. We compared the rats in the HGF-BM-MSC group with those in the other groups (rats treated with BM-MSCs, rats treated with HGF and untreated rats (Controls)) in detail. The localisation of EGFP-tagged BM-MSCs in the injured liver was evaluated using a microscope, and the cells co-expressed hepatocyte nuclear factor 4α, albumin and cytokeratin 18. After treatment for 4 weeks, the HGF-BM-MSC, BM-MSC and HGF groups exhibited increased protein and mRNA levels of hepatocyte nuclear factor 4α, albumin and cytokeratin 18, but decreased levels of aspartate aminotransferase, alanine aminotransferase and total bilirubin. These findings indicate that BM-MSC transplantation and HGF application have great potential for the treatment of hepatocirrhosis.