Abstract

Background. Liver fibrosis is a chronic progressive liver disease, but no established effective treatment exists except for liver transplantation. The present study was designed to investigate the effect of human placenta mesenchymal stem cells (hPMSCs) expressing green fluorescent protein (GFP) on carbon tetrachloride- (CCl4-) induced liver fibrosis in rats. Methods. Liver fibrosis was induced by subcutaneous injection with CCl4; hPMSCs were directly transplanted into rats through the caudal vein. The therapeutic efficacy of hPMSCs on liver fibrosis was measured by liver function tests, liver elastography, histopathology, Masson's trichrome and Sirius red staining, and immunohistochemical studies. The expression levels of fibrotic markers, transforming growth factor β1 (TGF-β1) and α-smooth muscle actin (α-SMA), were assessed using real-time polymerase chain reaction. Results. We demonstrated that liver fibrosis was significantly dampened in the hPMSC transplantation group according to the Laennec fibrosis scoring system and histological data. The Sirius red-stained collagen area and the elastography score were significantly reduced in the hPMSC-treated group. Meanwhile, hPMSC administration significantly decreased TGF-β1 and α-SMA expression and enhanced liver functions in CCl4-induced fibrotic rats. Conclusion. This study indicates that transplantation of hPMSCs could repair liver fibrosis induced by CCl4 in rats, which may serve as a valuable therapeutic approach to treat liver diseases.

Highlights

  • Liver fibrosis is a common chronic progressive liver disease caused by one or more etiologies such as viruses, alcohol, parasites, autoimmune reactions, long-term drug damage, or repeated effects of the formation of diffuse liver damage [1]

  • The Sirius red staining results revealed that the collagen-stained area in liver sections was more decreased in the human placenta mesenchymal stem cells (hPMSCs)-treated group than that in the untreated fibrosis group, and the collagen-stained area decreased with time in the hPMSC-treated group

  • We investigated the therapeutic effect of hPMSCs in a carbon tetrachloride- (CCl4-)induced rat liver fibrosis model

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Summary

Introduction

Liver fibrosis is a common chronic progressive liver disease caused by one or more etiologies such as viruses, alcohol, parasites, autoimmune reactions, long-term drug damage, or repeated effects of the formation of diffuse liver damage [1]. Liver fibrosis is a chronic progressive liver disease, but no established effective treatment exists except for liver transplantation. The present study was designed to investigate the effect of human placenta mesenchymal stem cells (hPMSCs) expressing green fluorescent protein (GFP) on carbon tetrachloride- (CCl4-) induced liver fibrosis in rats. Liver fibrosis was induced by subcutaneous injection with CCl4; hPMSCs were directly transplanted into rats through the caudal vein. The Sirius red-stained collagen area and the elastography score were significantly reduced in the hPMSC-treated group. HPMSC administration significantly decreased TGFβ1 and α-SMA expression and enhanced liver functions in CCl4-induced fibrotic rats. This study indicates that transplantation of hPMSCs could repair liver fibrosis induced by CCl4 in rats, which may serve as a valuable therapeutic approach to treat liver diseases

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