Preliminary Clinical Study on the Mscs Inducing Tolerance in Renal Transplantation
|School||Guangzhou Medical College|
|Keywords||Bone marrow mesenchymal stem cells Kidney transplant Immune tolerance|
Background: Kidney transplantation is the most effective method of treatment of end-stage renal disease, and need long-term use of immunosuppressive agents after transplantation. Immunosuppressive agents can not be completely avoided rejection, while increasing patient economic and psychological burden, but also increase the opportunities for infection, tumor, therefore looking for an effective way to reduce or even disable immunosuppressants majority of physician-patient staff the urgent need. Characteristics of bone marrow mesenchymal stem cells (Mesenchymal stem cells, MSCs) because of its tissue repair, immune regulation, and attention has been paid in transplantation tolerance applications, a class of cells become the most promising immunotherapy, at home and abroad have been a large number of in vitro and animal studies confirmed the role of MSCs in transplantation tolerance, but the lack of clinical trials, and the infusion of MSCs, dose, time point are inconclusive, to achieve the desired tolerance The state still faces huge challenges. Objective: by the transplant renal artery and postoperative intravenous infusion of bone marrow-derived mesenchymal stem cells in the kidney transplant surgery, after surgery to reduce the dosage of immunosuppressants. Observed normal circumstances, urine output, rejection rate, graft survival, monitoring of renal function, laboratory parameters, to explore the role and mechanism of the infusion of bone marrow-derived mesenchymal stem cells induce immune tolerance and to reduce the dose of immunosuppressants sex. Methods: random selection 2009-9-1 to 2009-12-31 our center underwent relatives living donor kidney transplant patients with chronic renal failure (uremia) patients were randomly divided into the infusion of bone marrow-derived mesenchymal stem cells experimental group and the infusion of bone marrow mesenchymal stem cells according to the group. Voluntary contributions from third-party health donor bone marrow MSCs strict aseptic separation, purification, amplification. Experimental group in living donor kidney transplant surgical procedures in transplant renal artery anastomosis mouth fixed a catheter to open the transplant renal blood flow, pressurized rapid infusion of bone marrow-derived mesenchymal stem cells transplant renal artery blood transfusion is 5 x 106, surgery after 1 menstrual peripheral intravenous infusion second bone marrow mesenchymal stem cells 2 × 106/kg, after long-term use of low-dose oral immunosuppressant tacrolimus (FK506) 0.05mg · kg -1 sup > · d -1 sup>, this alternate mycophenolate the ester (MMF) 20mg · kg -1 sup> · d -1 sup>, prednisone 15mg / day, the control group received standard doses of immunosuppressants, FK5060.08mg · kg -1 sup> · d -1 sup>, MMF20mg · kg -1 sup> · d -1 sup>, prednisone 15mg / day. Complications may occur after close observation and understanding of receptor immune recovery of graft function, monitoring of renal function, liver function, blood, FK506 concentration clinical indicators, to detect lymphocyte subsets, mixed lymphocyte reaction, cytokines status. Results: 6 patients during surgery goes well, one cases in the control group at 7 days after the transplant kidney area pain, no urine and serum creatinine levels, transplanted kidney ultrasound showed transplanted perirenal hematoma, the clinical diagnosis of acute renal allograft rejection, A strong dragon 0.25g, for three consecutive days, ATG100mg five consecutive days after treatment reverses renal function returned to normal. Control group: after 1 month serum creatinine average 88umol / L in March after an average 100umol / L,. Does not appear in the March transplanted kidney embolism, infection, graft-versus-host disease and other complications. Treg proportion preoperative average of 5.04%, after an average of 2.53% in January. CD19 CD5 B lymphocyte proportion preoperative average of 28.61%, after an average of 29.72 percent in January. An average of 60.6% of the CD19 CD27 B lymphocytes proportion preoperative, postoperative average of 47.29%. Proportion of NK cells preoperative average of 2.66%, after an average of 5.59%. Mixed lymphocyte culture stimulation index preoperative average 0.125, after an average of 0.3399. PMA-stimulated TNF-α preoperative average of 51.16%, after an average of 36.14 percent in January. IFN-γ preoperative average of 31.59%, after an average of 22.51 percent in January. IL -1 sup> 0 preoperative average of 1.81% in January after an average of 5.93. IL-4 preoperative average of 0.48%, after 1 month 1.98%. Experimental groups: intraoperative, postoperative bone marrow mesenchymal stem cell infusion process smoothly, good recovery of renal function. Postoperative serum creatinine average 131.3umol / L in March after an average of 134 umol / L in January. After transplantation in the transplant process did not occur embolism, infection, and graft-versus-host disease and other complications, renal allograft rejection did not occur. 5.78% average proportion of the experimental group Treg preoperative and postoperative average of 5.29% in January, the two cases were compared with the preoperative increase, higher than that of the control group. CD19 CD5 B lymphocytes preoperative average of 25.51%, after an average of 18.73 percent in January, compared with the control group decreased. CD19 CD27 B lymphocytes proportion preoperative average of 28.85%, postoperative average of 36.86%, the control group decreased. 10.1% average proportion of NK cells preoperative, postoperative average of 8.38%, the control group increased. Mixed lymphocyte culture stimulation index preoperative average 0.1003, in January after an average of 0.185, significantly lower than the control group. PMA stimulation experimental group, TNF-α preoperative average of 47.78%, after an average of 46.83%, including two cases of postoperative increase in the control group decreased. IFN-γ preoperative average of 27.51% in January after an average of 40.92 percent, decline in the control group. IL -1 sup> 0 preoperative average of 3.45%, after an average of 9.4% in January. IL-4 preoperative average of 0.86%, after 1 month 21.95%. Conclusion: Intraoperative transplant renal artery and after intravenous infusion of bone marrow-derived mesenchymal stem cells is safe and feasible; infusion of bone marrow mesenchymal stem cells can change the immune status of living donor kidney transplant recipients, can reduce the amount of immunosuppressive agents in patients .