Introduction: Data regarding stem cell infusion (SCI) for tolerance induction in renal transplantation (RTx) is sparse. We designed a prospective trial in a cohort of live-donor RTx (LDRT) patients subjected to pre-transplant SCI to test its tolerance promoting effects.
Material and methods: Ninety patients were subjected to pretransplant donor SCI of hematopoietic stem cells (HSC) and adipose tissue derived mesenchymal stem cells (AD-MSC) under non-myeloablative conditioning of Cyclophosphamide, rabbit-antithymocyte globulin and Rituximab with total lymphoid irradiation (TLI)/ Bortezomib for conditioning. Patients with diabetes, unwillingness, hepatitis C/B were excluded. Immune monitoring included donor specific antibodies (DSA) and peripheral regulatory T-cell (pTregs) [CD127lowCD25highCD4+]. Initial maintenance immunosuppression was calcineurin-inhibitor based to be discontinued with stable graft function and absence of rejection episodes. Graft biopsy was performed after 100 days of immunosuppression withdrawal (protocol biopsy) in willing patients/ for graft dysfunction. Rejections were treated by anti-rejection therapy followed by rescue immunosuppression.
Results: All immunosuppression except Prednisone has been successfully withdrawn for mean 2 years in 90 patients with mean age 32.2 years and donor-recipient HLA match, 2.81. Their mean Serum creatinine of 1.4 mg/dL and p-Tregs, 3.63% has remained stable after withdrawal. DSA are absent in 32%, present in 54.4% and reports awaited in 13.3% patients. Protocol biopsies in all 26 willing patients were unremarkable.
Conclusion: This is the first clinical report showing induction of T-regs with SCI leading to stable graft function in LDRT on low dose steroid monotherapy. MSC may serve as novel, safe and effective immunomodulators in clinical transplantation.
To cite this abstract in AMA style:Trivedi H, Vanikar A, Kute V, Patel H, Gumber M, Shah P, Dave S, Trivedi V. Pretransplant Infusion of Donor Stem Cells Open Gateway to Tolerance through Induction of Regulatory T Cells and Activation of Other Allosuppressive Immune Mechanisms – Single Centre Experience in Living Donor Renal Transplantation [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/pretransplant-infusion-of-donor-stem-cells-open-gateway-to-tolerance-through-induction-of-regulatory-t-cells-and-activation-of-other-allosuppressive-immune-mechanisms-single-centre-experience/. Accessed August 20, 2019.
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