ABSTRACT
The technique of stem cells or hepatocytes transplantation has recently improved in order to bridge the time before whole-organ liver transplantation. In the present study, unfractionated bone marrow stem cells (BMSCs) were harvested from the tibial and femoral marrow compartments of male mice, which were cultured in Dulbecco's modified Eagle's medium (DMEM) with and without hepatocyte growth factor (HGF), and then transplanted into Schistosoma mansoni-infected female mice on their 8th week post-infection. Mice were sacrificed monthly until the third month of bone marrow transplantation, serum was collected, and albumin concentration, ALT, AST, and alkaline phosphatase (ALP) activities were assayed. On the other hand, immunohistopathological and immunohistochemical changes of granuloma size and number, collagen content, and cells expressing OV-6 were detected for identification of liver fibrosis. BMSCs were shown to differentiate into hepatocyte-like cells. Serum ALT, AST, and ALP were markedly reduced in the group of mice treated with BMSCs than in the untreated control group. Also, granuloma showed a marked decrease in size and number as compared to the BMSCs untreated group. Collagen content showed marked decrease after the third month of treatment with BMSCs. On the other hand, the expression of OV-6 increased detecting the presence of newly formed hepatocytes after BMSCs treatment. BMSCs with or without HGF infusion significantly enhanced hepatic regeneration in S. mansoni-induced fibrotic liver model and have pathologic and immunohistopathologic therapeutic effects. Also, this new therapeutic trend could generate new hepatocytes to improve the overall liver functions.
Subject(s)
Animals , Female , Male , Mice , Alanine Transaminase/blood , Alkaline Phosphatase/blood , Antigens, Differentiation/biosynthesis , Aspartate Aminotransferases/blood , Bone Marrow Cells/cytology , Bone Marrow Transplantation , Cell Differentiation , Cell- and Tissue-Based Therapy , Cells, Cultured , Collagen/metabolism , Granuloma/parasitology , Hepatocyte Growth Factor/pharmacology , Hepatocytes/cytology , Liver/parasitology , Liver Cirrhosis/parasitology , Mice, Inbred BALB C , Schistosoma mansoni/pathogenicity , Schistosomiasis mansoni/mortality , Stem Cell Transplantation , Stem Cells/cytologyABSTRACT
Objective To explore the relationship between hepatic stem cells and hematopoietic stem cells by detecting the expression of OV6 and CD34 in rat hepatic oval cells. Methods Healthy SD rat were fed with chemical carcinogen 3’-me-DAB for 4 weeks, then the rat hepatic tissue samples were obtained. The rats fed with normal forage served as normal controls. The expressions of OV6 and CD34, specific markers for oval cells and hematopoietic stem cells respectively, in rat hepatic stem cells were detected by immunocytochemical staining (ABC method). Results The oval cells positive for OV6 and CD34 were found in the limiting plate of portal area, mainly located around the Hering canal. In addition, some oval cells positive for OV6 and CD34 were found migrating to hepatic lobule, scattering in the hepatic cords. A great many mononuclear stem cells positive for OV6 and CD34 were also found in the hepatic parenchyma. Conclusion 3’-me-DAB could stimulate the proliferation of hepatic oval cells and hematopoietic stem cells and cause the hematopoietic stem cells derived from bone marrow to migrate to hepatic parenchyma and differentiate.