Allograft tolerance induction by isogeneic bone marrow mesenchymal stem cells transfusion in heart transplant rats / 中华器官移植杂志

ABSTRACT

Objective To induce the immune tolerance of heart grafts with infusion of isogeneic bone marrow mesenchymal stem cells (BMSCs) in heart transplant rats.Method Donor Wistar rats and recipient F344 rats were randomly divided into 4 groupsacute rejection group (group A),Wistar rats as the donors and F344 rats as the recipients for heart transplantation; low dose cyclosporin A(CsA) group (group B),recipient F344 rats given low dose CsA; BMSCs group (group C),recipient F344 rats given isogeneic BMSCs; BMSC and low dose CsA group (group D),the recipient F344 rats given isogeneic BMSCs and low dose CsA.The serum cytokine levels were determined,and the donor heart pathological changes and survival were observed postoperatively.The relative level of Foxp3 mRNA expression in the spleen of the recipient F344 rats was also observed.Result The blood levels of interleukin-2 (IL-2) and interferon-γ(INF-γ) were significantly reduced,but IL-4 and IL-10 levels were increased (P＜0.05),and the survival time of donor heart was significantly prolonged in group D as compared with groups A,B and C (P＜0.05 for all).Heart pathological examination revealed a mild acute rejection in group D,moderate acute rejection in groups B and C group,and severe acute rejection in group A respectively.The expression of Foxp3 mRNA was significantly lower in group A than in groups B,C and D (P＜0.05 for all),and that in group D was significantly higher than in groups B and C (P＜0.05 for both),but there was no significant difference between between groups B and C (P＞0.05).Conclusion Intravenous administration of BMSCs can alleviate immunorejection in heterotopic rat heart transplantation.Low-dose CsA acts synergistically with BMSCs to significantly inhibit acute rejection after heart transplantation.The partial mechanisms involve the suppressive effect of BMSCs on the expression of Foxp3 mRNA and modulation on cytokine.