Induction of immune tolerance using kidney-bone marrow transplantation: Does it promote chimerism formation? / 中国组织工程研究

ABSTRACT

BACKGROUND: Infusion of hemopoietic stem cell from donors can promote the chimeric formation and induce specific immunologic tolerance in the allograft recipients. However, the pretreatment for cell transplantation has great toxicity to recipients. So immunosuppressant combined bone marrow infusion is introduced to anti graft versus host reaction. OBJECTIVE: Based on microchimerism, to study the security and associativity of chimera formation induced by kidney-bone marrow transplantation and immunologic tolerance.DESIGN, TIME AND SETTING: The contrast observation was performed at the department of urinary surgery, The Third People's Hospital of Zhengzhou City from January 1998 to December 2005.PARTICIPANTS: According to ABO/Rh blood type and HLA matching, 96 female patients with chronic renal failure and waiting for kidney transplantation were divided into 2 groups, In the combination group, patients received kidney combined bone marrow transplantation; the other uremia patients received the other kidney of cadavers were served as control group. The donors were 48 healthy males. METHODS: Bone marrow of donors was collected simultaneously with kidney obtain and preserved with cryoprotectant at -198 ℃ in nitrogen canister. After kidney transplantation, large dose of anti-human lymphocyte immune globulin were used for 2 weeks, then (0.9-2.5)×10~8/kg mononuclearcell was reinfused. PCR-SRY was used to identify donor derived cell-chimerism. Lymphocyte subgroup of recipients was determined by blood test; and interleukin 10 was measured by enzyme linked immunosorbent assay; in addition, the mass concentration of tumor necrosis factor α and tumor necrosis factor β was detected. MAIN OUTCOME MEASURES: Chimerism, lymphocyte subsets and cytokines were detected at various time points following transplantation. Simultaneously, the transplantation results and complication status of recipients were observed. RESULTS: The positive rate of chimera in the combination group was greater than that of the control group (P < 0.05). The 3-year follow-up showed that incidence differences of acute rejection between recipients with positive chimera and recipients with negative chimera had significance (13%, 35%, P < 0.05). There was no graft versus host disease occurred in the combination group. CONCLUSION: Kidney-bone marrow transplantation can augment chimerism in early postoperative period, and significantly reduce the rate of acute rejection, which is safe and beneficia1to induce specific immunologic tolerance in the renal allograft recipients.