Effect of co-transplantation of mesenchymal stem cells and hematopoietic stem cells as compared to hematopoietic stem cell transplantation alone in renal transplantation to achieve donor hypo-responsiveness.

INTRODUCTION: We evaluated donor hypo-responsiveness in renal allograft recipients to donor adipose tissue-derived mesenchymal stem cell (h-AD-MSC) +hematopoietic stem cell transplantation (HSCT) vs. HSCT alone. METHODS: Patients were divided into 2 demographically equal groups (n = 100) A and B subjected to equal non-myeloablative conditioning of target-specific irradiation, anti-T + B cell antibodies and cyclophosphamide with HSCT. Group A was administered h-AD-MSC additionally. Transplantation was performed following favorable cross-matching. Cyclosporine, 3 mg/kg BW/day + prednisone, 20 mg/day were immunosuppressants for first 3 months, cyclosporine was replaced by azathioprine subsequently and prednisone lowered to 5-10 mg/day. Peripheral blood chimerism (PBC) was studied using fluorescent in situ hybridization technique at 3/18 months post transplant. Biopsy was performed for graft dysfunction and reported as per Banff criteria,'05. RESULTS: Mean nucleated HSC counts (n × 10(8)/kgBW) was 7.32 with mean CD34+ yield 0.09% in group A; and 6.98 and 0.40% in group B, respectively; CD45-/90+ was 13.49% in former. Over 18 months post transplant, former had mean serum creatinine (SCr), 1.59 mg%, 12% acute rejection (AR) episodes, 3% patient, 1% patient +graft loss; latter had mean SCr 1.49 mg%, 18% AR episodes, 1% patient, 6% graft and 8% patient +graft losses. PBC was higher (4%) in former than later (1.8%). CONCLUSION: Combined h-AD-MSC +HSCT under non-myeloablative conditioning was safe, more effective than HSCT alone to achieve donor hypo-responsiveness with adequate stable graft function and reduced rejection episodes.