| Background Renal transplantation is the most effective treatment for end stage renal disease( ESRD). The immunosuppressive drugs can not completely avoidrejection, but increase patients'economic and psychological burden. The chancesof infection, and malignancies are also increased. Thus, to find an effective way to reduce or remove immunosuppressant is an urgent need for majority of medicalstaff. Mesenchymal stem cells emerged as a promising cell for immunomodulatorytherapy. because of it's characteristics such as tissue repair, immune regulationand immune tolerance etc. Presently there has been a large number of in vitro andanimal studies which validate the MSCs'role in transplantation tolerance, but clinical trials are exile. The infusion, method, dose and time point are inconclusive, to meet the ideal state of immune tolerance is still facing great challenge.Objective To investigate the role and mechanism of MSCs in induction of immunetolerance and the feasibility of reducing immunosuppressants by monitoring urine volume, rejection rate, graft survival, renal function, laboratory indicators etcof recipients after twice MSCs infusion and reduced dosage of immunosuppressiveagents.Methods From 2009-9-1 to 2009-12-31, six cases of patients in our center were randomly divided into two groups: Experimental group infusion of bone marrowmesenchymal stem cells and with Control group, without infusion of MSCs. MSCs are produced from healthy third party donor's bone marrow, which experienced sterile separation, purification and amplification. Experimental group had received twice MSCs infution : the first time of infution is during operation, with dose 5×106when renal blood flow was open, through the catheter fixed in renal arteryanastomosis by compression. The second time of infusion was through peripheral vein whth the dose of 2×106/kg 1 month later.The patients in experimented group received low-dose oral immunosuppressive agents after transplation(FK5060.05 mg·kg-1·d-1, MMF20 mg·kg-1·d-1, Prednisone 15mg per day); the control group was given standard doses of immunosuppressive agents(FK5060.08 mg·kg-1·d-1, MMF20 mg·kg-1·d-1, Prednisone 15mg per day). In order to understand the immune status of the recipients,the possible complications, post-transplant renal function, hepatic function etc were closely observed, the recipients'indicators such as lymphocyte subsets, mixed lymphocyte culture and levels of cytokines were monitored.Results The operation processes of 6 patients were smoothly. In the control group, one case was clinically diagnosed with AR by anuria, higher CRE , hypogastralgia, and perirenal hematoma showed by at the 7th days after renal transplantation, which is reversed by the therapy of MP 0.25g for 3 days,and ATG 100mg for 5 days, renal function returned to normal. Control group: Average CRE is 88umol/L 1 month after operation, 100umol/L three months after operation. There were on thrombosis, infection, graft versus host disease and other complicationsoccurred in the recipients. The average natio of Treg proportion was 5.04% before operation, 2.53% 1 month after operation. The average ratio of CD19+CD5+ B cell was 28.61% versus 29.72%. CD19+CD27+ B cell was 60.6% versus 47.29%, NK cell was 2.66% versus 5.59%.,The average SI in MLR was 0.215 before operation, 0.3399 afteroperation. The average level of TNF-αwas 51.16% versus 36.14% . IFN-γwas 2.66% versus 5.59%. IL-10 was 1.81% versus 5.93%. IL-4 was 0.48% versus 1.98%.Experimental group: process of MSCs infusion was smooth, renal function was good. Average level of CRE was 131.3umol/L 1 month after operation, 134umol/L three months after operation. The recipients were without thrombosis, infection, graft versus host disease,other complications, and acute rejection. The average ratio of Treg proportion was 5.78% before operation, 5.29% 1 month after operation, Treg level after operation was higher than that of control group with 2 patients. The average ratio of CD19+CD5+ B cell was 25.51% before operation, 18.73% after operation, less than that of control group. The average ratio of CD19+CD27+ B cell was 28.85% versus 36.86%. NK cell was 10.1% versus 8.38%. SI in MLR was 0.1003 versus 0.185. TNF-αwas 47.78% versus 46.83%. IFN-γwas 27.51% versus 40.92%. IL-10 was 3.45% versus 9.4%. T IL-4 was 0.86% versus 21.95%.Conclusion Infusion of bone marrow mesenchymal stem cells through renal artery during transplantation and through peripheralvein after transplantation is safety and practicable. Infusion of MSCs can change the immune status of living donor kidney transplant recipients and may reduce the dosage of immunosuppressant.
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