Study On The Induction Of Immune Tolerance In Rat Kidney Transplantation By Hematopoietic Stem Cell

Objectives:Achieving immunological tolerance,a state of donor-specific unresponsiveness,remains a paramount goal in organ transplantation. Successful application would allow for allogeneic transplantation without the toxic effects of nonspecific immunosuppression and curb the high rates of graft loss due to acute and chronic rejection.We designed an animal study to induce immune tolerance in recipient rats of allogenic kidney transplantation with hematopoietic stem cells and to study the mechanism of the tolerance.Methods:1.A model of renal transplantation was established.Intravenous stent was inserted from the distal end to the donor's left renal vein and further into the lumen of the recipient's left renal vein.End-to-side anatomosis of both renal aortas was performed.Urinary tract reconstruction was accomplished by suturing the donor ureter with a bladder patch to the recipient bladder.2.Study on the induction of immune tolerance in renal transplantation by hematopoietic stem cell:(1) Kidney transplantations were performed in 32rats. (2) Wistar rats were treated TLI before surgery,then HBC were injected to receptors.Renal transplantation was performed within the same day.(3) The survival days of receptor rats were observed.Serum creatinine was measured and color Doppler flow imaging was checked.The immunologic tolerance status was detected by MLR of 30th day receptor rat spleen cells cultured with the donor spleen cells and the third party.Results:1.Kidney transplantations were performed in 30rats.The pathological examinations showed that There model was failure due to hemorrhage of anatomosis of both renal aortas.Two models was failure due to thrombus of anatomosis of both renal aortas.Two models was failure due to overdose of anesthesia,achievement ratio of this model is 76.7%.2.The mean survival time of case group(D group) was 58.9d,The difference was significant between case group and other three control groups.3.Serum creatinine of control group(A group) went up quickly after resection of self-kidney,serum creatinine of B and C group went up smoothly after resection of self-kidney,but serum creatinine of case group was stable after resection of self-kidney.4.There was no acute rejection in B and C group,interstitial edema necrosis and ablate of renal tubular epithelial cell were not obviously. Lymphocyte soakage,interstitial edema necrosis and ablate of renal tubular epithelial cell were not found in case group.5.Blood supply of control group(A group) was badly,resistent index(RI) was＞0.7.Blood supply of case group(A group) was abundant,resistent index(RI) was between 0.3～0.6.The difference was significant between case group and A groups.6.Recipients of this group show a low response to donor specific spleen cells when MLR are observed,but a hypore-sponsiveness to donor occurred while the normal reaction to the third parity was retained.Conclusion:1.This modified rat model of renal transplantation is simple,economical, reliable,stable with higher success rate and can be applied in the experiment of renal transplantation research.2.The hematopoietic stem cells can induce donor-specific tolerance from allograft.