幹細胞研究と治療のジャーナル

概要

Regulatory T-Cells Support Stem Cell Therapy in Safe Minimization of Immunosuppression in Living Donor Renal Transplantation

Hargovind Trivedi, Aruna Vanikar, Himanshu Patel, Vivek Kute and Shruti Dave

Background: Stem cell therapy (SCT) has encouraging results in tolerance induction in living-donor renal transplantation (LDRT). T-regulatory cells [CD4+CD25highCD127neg/low] promote tolerogenicity. We report initial experience of LDRT using SCT with Tregs.
Material and methods: In this prospective study of demographically well-balanced 3 groups of 30 LDRT patients each, group-1 underwent donor hematopoietic stem cell (HSC) and adipose-tissue-derived mesenchymal stem cell (AD-MSC) infusion in thymic and portal circulation under non-myeloablative conditioning pre-transplant, and Treg infusion posttransplant, group-2 received SCT alone, and group-3 were transplanted with standard triple immunosuppression. Tregs were derived from co-cultured donor AD-MSC and recipient peripheral mononuclear cells. Maintenance immunosuppression was low dose Tacrolimus + prednisone in groups-1 and 2.
Results: Mean infused CD34+ (N x106/kgBW) were 2.7 in group-1, 2.2 in group-2, ADMSC (N x104/kgBW), 1.37 in group-1 and 1.34 in group-2, and Tregs (N x104/kgBW) were 2.21. There were no untoward effects of SCT. Over mean follow-up of 19.34 months in group-1 and 20.6 months in group-2 there was 100% patient + graft survival. In group-3 over a mean follow-up of 20.55 months, there was 100% patient survival and 93.3% graft survival. Their mean serum creatinine (mg/dL) was 1.35, 1.4 and 1.3 respectively. There were 2 acute rejection episodes in group-1, 5 in group-2 and 7 in group-3, and 1 chronic rejection in group-3. Severity was more in group-3. Tregs in periphery were 3.63% in group-1, 3 % in group-2 and 1.9% in group-3.
Conclusion: Tregs support SCT in safe minimization of immunosuppression in LDRT.