An Experimental Study Of Tolerance To Cardiac Xenograft Induced By The Mixed Xenogeneic Chimera

OBJECTIVES: To explore the mechanisms of tolerance in xenograft induced by establishing the guinea pig to rat mixed chimeras model with a non-myeloabalative preparative regimen.METHODS: Recipient SD rat were conditioned with sublethal whole body irradiation (WBI) ,divided randomly into three groups, followed by infusion of 0.8ml liquid within 4 h . Group A infused guinea pig bone marrow cells (BMC); Group B infused bone marrow mesenchymal stem cells (BM-MSCs); Group C infused saline solution. then were administered cytoxan(CTX) intraperitoneal injection. The change of INF-γ, IL-4 and IL-10 of the recipient after cell transplantation was detected by ELISA .To explore tolerance mechanisms by performing mixed lymphocyte reaction (MLR) and detecting the percentage of donor origin cells in the peripheral blood lymphocyte of recipient rats. The grafted heart mean survival time (MST)and the pathology were observed by using Chinese Cobra Venom Factor (CVF) on the established guinea pig to rat mixed xenogeneic chimera cardiac xenograft model.RESULTS: Guinea pig lymphoid chimeras can be found in the peripheral blood lymphocyte of the tolerance SD rat (Group A> Group B). The expression levels of (these cytokines) INF-γ, IL-4 and IL-10 in the tolerance SD rat all increased slightly, then returned to basal levels. Recipient SD rat were specifically tolerant to the guinea pig in MLR assay. Pathology: Group A showed hyperacute rejection (HAR) after cardiac transplantation. The survival time of xenograft in Group ACVF ranged from 316 to 400 minutes. There were significant difference among Group ACVF compared with Group CCVF and D (P < 0. 01).CONLUSIONS: Non-myeloablative conditioning regimens for allogeneic BMC/BM-MSCs transplantation can successfully establish guinea pig→rat mixed chimeras model and induce a specific tolerance in SD rat to guinea pig. Mixed xenogeneic...