Histological study on the effect of stem cells and hepatocyte growth factor on induced liver fibrosis in male albino rats

Abstract

Background Liver fibrosis is a major Egyptian health problem. Hepatic stellate cells are the pivotal cells in the pathogenesis of liver fibrosis. Mesenchymal stem cells (MSCs) and hepatocyte growth factor (HGF) participate in liver fibrosis treatment; chitosan nanoparticles (CNPs) provide effective delivery of HGF to its niche. Aim of work The aim of the study was to compare the effect of MSCs and HGF, either separately or mixed together, in improving liver fibrosis using a rat model of thioacetamide (TAA)-induced liver injury. Materials and methods Sixty male albino rats were used in this work. They were divided into the control group and the TAA-induced fibrosis group, which was further subdivided into the untreated fibrosis group, the MSC-treated group, the HGF-incorporated CNP (HGF–CNP)-treated group, the MSCs+HGF–CNP-treated group, and the CNP-treated group. The livers were removed from sacrificed rats and processed for staining with H&E and Masson’s trichrome and for immunohistochemical staining for α-smooth muscle actin (α-SMA) and proliferating cell nuclear antigen (PCNA). Results The present study revealed that MSCs when mixed with HGF–CNP have a potent effect in improving TAA-induced liver fibrosis as regards restoration of the normal hepatic architecture and decreased collagen fiber content; positive α-SMA immunoreaction was decreased with few immunoreactive hepatic stellate cells between hepatocytes. Many hepatocytes exhibited positive nuclear immunoreactivity for proliferating cell nuclear antigen. There was moderate improvement in the effect of MSCs or HGF–CNP alone. In contrast, CNPs achieved slight improvement in TAA-induced liver fibrosis. Conclusion Coinjection of MSCs and HGF–CNP has a better therapeutic effect on liver fibrosis in rats compared with either one alone. This mode of therapy, if proved to be effective in humans, may provide a perfect alternative to liver transplantation.