title: Amelioration of Murine Schistosoma mansoni Induced Liver Fibrosis by Mesenchymal Stem Cells.
abstract: 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.
authors.affiliation: Departments of Medical Biochemistry, Unit of Biochemistry and Molecular Biology and Histology .
authors.forename: Mt
authors.initials: M
authors.lastname: Abdel Aziz
authors.affiliation: Departments of Medical Biochemistry, Unit of Biochemistry and Molecular Biology and Histology .
authors.forename: Hm
authors.initials: H
authors.lastname: Atta
authors.affiliation: Departments of Medical Biochemistry, Unit of Biochemistry and Molecular Biology and Histology .
authors.forename: Nk
authors.initials: N
authors.lastname: Roshdy
authors.affiliation: Departments of Medical Biochemistry, Unit of Biochemistry and Molecular Biology and Histology .
authors.forename: LA
authors.initials: L
authors.lastname: Rashed
authors.affiliation: Departments of Medical Biochemistry, Unit of Biochemistry and Molecular Biology and Histology .
authors.forename: D
authors.initials: D
authors.lastname: Sabry
authors.affiliation: Departments of Medical Biochemistry, Unit of Biochemistry and Molecular Biology and Histology .
authors.forename: Aa
authors.initials: A
authors.lastname: Hassouna
authors.affiliation: Faculty of Medicine, Cairo University , Cairo, Egypt .
authors.forename: Gi
authors.initials: G
authors.lastname: Aboul Fotouh
authors.affiliation: Departments of Medical Biochemistry, Unit of Biochemistry and Molecular Biology and Histology .
authors.forename: Nm
authors.initials: N
authors.lastname: Hasan
authors.affiliation: Departments of Medical Biochemistry, Unit of Biochemistry and Molecular Biology and Histology .
authors.forename: Rh
authors.initials: R
authors.lastname: Younis
authors.affiliation: Departments of Medicine and Genetics, Albert Einstein College of Medicine , Bronx, NY, USA .
authors.forename: Jr
authors.initials: J
authors.lastname: Chowdhury
keywords: MMP;; MSCs;; S. mansoni;; TIMP; liver fibrosis;