Schistosomiasis is a common chronic helminthic
infection of the liver that causes hepatic
fibrosis and
portal hypertension,contributing to the death of over half a million people a year. Infusion of autologous bone marrow cells into patients with
hepatic cirrhosis has been reported to ameliorate symptoms of
portal hypertension and improve liver function, either by conversion of the infused mesenchymal stem cells (MSCs) to hepatocytes or by modulating of the hepatic
fibrosis. Here,we have investigated the antifibrotic effect of mesenchymal stem cells (MSCs) using S. mansoni-induced
liver fibrosis in mice, which causes an intense, stable
fibrosis. MSCs derived from bone marrow of male mice were then infused intravenously into female mice that had received
intraperitoneal injection of S.mansoni cercariae. Mice were divided into 4 groups: Untreated control; MSCs infusion only;
Schistosomiasis only; and
Schistosomiasis plus MSCs infusion. Serum
alanine aminotransferase (ALT) and liver histopathology were evaluated. Expression of the
collagen gene (type I),
transforming growth factor (TGF-β),
matrix metalloproteinase (MMP2),
tissue inhibitor of metalloproteinase (TIMP-1),stromal cell-derived factor-1(SDF-1) and its
receptor (CXCR4) were analyzed. MSC infusion resulted in significant decrease in liver
collagen and TGF-β gene expression in the
Schistosomiasis mice. The ratio of MMP-2 to
TIMP-1 expression increased. SDF-1 and CXCR4
mRNA expression also increased. There was overall improvement of liver histology and a statistically significant reduction of serum ALT level. MSCs infusion ameliorated S. mansoni-induced
liver fibrosis, probably by modulating the relative expression of
MMP and TIMP. The findings support the hypothesis that MSCs participate in liver regeneration and functional improvement by reducing
liver fibrosis.