Bone Marrow Mesenchymal Stem Cells Can Attenuate Acute Kidney Injury Following Cardiopulmonary Bypass In Rats

ObjectiveTo investigate the protective effects and mechanisms of bone marrow mesenchymal stem cell(MSC) on acute kidney injury(AKI) following cardiopulmonary bypass(CPB) in rats.Methods:1. Primary isolation, culture and purification of MSC from eGFP (enhanced green fluorescent protein transgenic) rats.2. Seventy-two male Sprague-Dawley rats weight between (288.8+26.1) g were divided into three groups:sham group, CPB group and CPB+MSC group. The CPB group underwent 60 minutes cardiopulmoanry bypass, while the CPB+MSC group were injected with 1.5*106 MSCs via right external jugular after the operation. The same surgical manipulation was performed in sham group except no CPB conducted. Serum and renal specimens were collected at 6h,24h and 48h after the CPB. The serum Cr, IL-10 and IL-6 were analyzed by ELISA, the expression of vascular endothelial growth factor (VEGF) and insulin-like growth factor 1 (IGF-1) in renal tissues were detected by Western blot, the histopathologic changes of kidneys and homing positions of eGFP-MSCs were examined by pathological sections.Results:1. The eGFP-MSCs were isolated and purified successfully, the morphology of cells sticking on plastic formed whirlpool shape, spindle like and relatively uniform were observed at third generation. A great quantity of cells with green fluorescence can be found when examined at the fluorescent microscope and the expression of surface antigen CD34, CD90, CD45 and CD29 was 99.74%,98.01%,0.16% and 14.09% respectively.2. The CPB-AKI rat models were established (survival rate> 90%). When compared with CPB group, the serum Cr, IL-6 and IL-10 in CPB+MSC group were ameliorated and the expression of VEGF and IGF-1 in renal tissues were increased significantly. The pathological injury of renal tubular was ameliorated in MSC+CPB group, and a large number of MSCs were accumulated in lung tissues, while only few MSCs homing in kidneys found at 6 hours.Conclusion:1. The CPB-AKI models were established successfully on the weight (288.8±26.1) g male SD rats through the right jugular vein and femoral artery cannulation.2. The transplantation of MSCs can alleviate kidney injury caused by CPB. The protective effects of MSC were implemented mainly by its paracrine secretion of anti-inflammatory cytokines and cytoprotective factors, which could have functions on immunoregulation and cell proliferation.