Abstract
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.
Highlights
Transplantation is well accepted therapy for end organ failure
There were no untoward effects of Stem cell therapy (SCT)
No infections/adverse side effects including graft versus host disease (GVHD) were observed in groups 1 and 2
Summary
Transplantation is well accepted therapy for end organ failure. It has its own disadvantages in the form of life-long immunosuppression to prevent rejection of the grafted organ. It is a well-known fact that graft survival improves significantly with better HLA-matched donor. We have been using stem cell therapy (SCT) for safe and effective minimization of immunosuppression in living donor renal transplantation (LDRT) [5]. This study aims to present our initial experience of infusing in vitro generated T-regulatory cells (T-regs) in LDRT. Stem cell therapy (SCT) has encouraging results in tolerance induction in living-donor renal transplantation (LDRT). We report initial experience of LDRT using SCT with Tregs
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