Preliminary Study of Bone Marrow-Derived Mesenchymal Stem Cells Pretreatment With Erythropoietin in Preventing Acute Rejection After Rat Renal Transplantation

摘要

Renal transplantation is currently the most effective treatment for end-stage kidney diseases, and acute allograft rejection is well treated with high dose prednisolone and immunosuppressive agents, but long-term use of immunosuppressants will be detrimental to the long-term survival of the transplanted kidney and will have many side effects on the human body. Thus, a local and alloantigen-specific immunological tolerance may be a promising approach to improving kidney transplantation. The aim of this study is to examine the therapeutic potential of transforming bone marrow-derived mesenchymal stem cells (BMSCs) pretreated with erythropoietin (EPO) in inducing immunosuppression in renal grafts after transplantation. The immunity suppression effects were tested, focusing on the decrease of serum creatinine and the cells' ability to regulate the expression of the cytokines associated with acute rejection. Our findings demonstrate that a transfusion of BMSCs pretreated with EPO (EPO-BMSCs) can produce an immunosuppressive effect and reduce the occurrence of acute rejection. Their reciprocal effects on the induction and function of regulatory T cells (Tregs) resulted in the balance of IFN-γ/IL-4 and improved immunosuppressive effects in local kidney grafts. Our data also suggest that the acute rejection microenvironment had a directional chemotactic effect on BMSCs, which is related to the upregulation of CXCR4, and could be further enhanced by EPO treatment. Thus, transfusion of EPO-BMSCs can induce a greater local immunosuppressive effect in renal grafts after transplantation compared with untreated BMSCs. Therefore, transplantation with EPO-BMSCs can be a novel and effective approach to lower the acute rejection ratio following transplantation.