Stem cell therapy facilitates tolerance in renal transplantation

Abstract

Background: Strategies for tolerance induction (TI) include induction of chimerism and/or clonal deletion. We present 5-year experience of TI in living-donor related renal transplantation (LDRT) using adipose derived mesenchymal stem cell (AD-MSC) and hematopoietic SC (HSC) infusion with supportive therapy. Methods: Twenty patients divided in 2 equal, demographically balanced groups underwent LDRT under TI protocol (TIP) consisting of conditioning with Bortezomib, Methyl prednisone, rabbit-anti-thymoglobulin and Rituximab. Group-1 were administered in-vitro generated AD-MSC and HSC, group-2 were administered donor specific transfusion. Transplantation was carried out with acceptable lymphocyte cross-match, T and B-cell flow cross-match, single antigen assay and negative mixed lymphocyte reaction (MLR). No conventional immunosuppression was to be administered. Monitoring included serum creatinine (SCr-mg/dL), donor specific antibodies (DSA) and MLR. Protocol biopsies were planned after 100 days and yearly in willing patients. In event of rejection/ DSA/ MLR, rescue immunosuppression was planned. Results: Over mean 5.4 (range: 4.9-6.3) year follow-up patient survival was 80% in group-1 and 90% in group-2; deathcensored graft survival was 90% in group-1 and 70% in group-2. Mean SCr was 1.52 in group-1, and 1.97 in group-2. Five patients from group-1 and 3 from group-2 were on no conventional immunosuppression, 2 patients of group-1 and 1 of group-2 were on two immunosuppressants and 1 patient of group-2 was on 3 immunosuppressants. DSA appeared in 2 patients of group-1 without affecting graft function and 4 of group-2 causing graft dysfunction. MLR was negative in both groups. Conclusion: SCs facilitate TI in LDRT under non-myeloablative conditioning.