Effects of bone marrow mesenchymal stem cell transplantation on CD4+CD25+regulatory T cells in rats with primary nephrotic syndrome / 中国组织工程研究

ABSTRACT

BACKGROUND:Decreased function and reduced number of CD4+CD25+regulatory T cells have been considered the major manifestation of immunity dysfunction in children with primary nephrotic syndrome. Bone marrow mesenchymal stem cells have immunoregulation effects, which up-regulate CD4+CD25+regulatory T cells, inhibit proliferation of lymphocytes, and have been widely used in many immune diseases. OBJECTIVE:To investigate the effects of bone marrow mesenchymal stem celltransplantation on the CD4+CD25+regulatory T cells of peripheral blood in rats with primary nephrotic syndrome. METHODS:Bone marrow mesenchymal stem cells from six Sprague-Dawley rats were isolated, passaged and utilized for cellsuspension preparation. At the third passage, bone marrow mesenchymal stem cells were used for transplantation. The remaining 30 rats were randomly and equal y divided into three groups:normal group, normal saline infusion group, and bone marrow mesenchymal stem cells group. The rat models of primary nephrotic syndrome were established by single injection of adriamycin intravenously through tail vein in the latter two groups. Rats were then treated with bone marrow mesenchymal stem cells (1×10 7 ) (bone marrow mesenchymal stem cells group) or normal saline (normal saline infusion group) through tail vein at the same time after adriamycin administration. The normal group received no treatment. RESULTS AND CONCLUSION:Compared with the normal group, rats in the normal saline infusion group developed nephropathy characterized by ascites, proteinuria, hypoalbuminemia, hypercholastero-lnemia, and progressive renal injury. However, the proteinurine and clinical severity in bone marrow mesenchymal stem cells group were significantly ameliorated after treatment with bone marrow mesenchymal stem cells. CD4+CD25+Treg/CD4+Treg in the peripheral blood in the bone marrow mesenchymal stem cells group and normal saline infusion group were significantly higher than that in the normal group at 28 days after model establishment (P0.05). The expression of FoxP3 mRNA in the peripheral blood mononuclear cells of the bone marrow mesenchymal stem cells group was significantly higher than that in the normal saline infusion group and normal group (P<0.05). The bone marrow mesenchymal stem cells play a protective effect in rats with primary nephrotic syndrome, which may be related to the increase of local expression of FoxP3 and generation of CD4+CD25+Treg.