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Bone marrow-derived mesenchymal stromal cells (MSC) have emerged as useful cell population for immunomodulation therapy in transplantation. Moving this concept towards clinical application, however, should be critically assessed by a tailor-made step-wise approach. Here, we report results of the second step of the multistep MSC-based clinical protocol in kidney transplantation. We examined in two living-related kidney transplant recipients whether: (i) pre-transplant (DAY-1) infusion of autologous MSC protected from the development of acute graft dysfunction previously reported in patients given MSC post-transplant, (ii) avoiding basiliximab in the induction regimen improved the MSC-induced Treg expansion previously reported with therapy including this anti-CD25-antibody. In patient 3, MSC treatment was uneventful and graft function remained normal during 1 year follow-up. In patient 4, acute cellular rejection occurred 2 weeks post-transplant. Both patients had excellent graft function at the last observation. Circulating memory CD8+ T cells and donor-specific CD8+ T-cell cytolytic response were reduced in MSC-treated patients, not in transplant controls not given MSC. CD4+FoxP3+Treg expansion was comparable in MSC-treated patients with or without basiliximab induction. Thus, pre-transplant MSC no longer negatively affect kidney graft at least to the point of impairing graft function, and maintained MSC-immunomodulatory properties. Induction therapy without basiliximab does not offer any advantage on CD4+FoxP3+Treg expansion (ClinicalTrials.gov number: NCT 00752479).

Mesenchymal stromal cells and kidney transplantation : pretransplant infusion protects from graft dysfunction while fostering immunoregulation / N. Perico, F. Casiraghi, E. Gotti, M. Introna, M. Todeschini, R.A. Cavinato, C. Capelli, A. Rambaldi, P. Cassis, P. Rizzo, M. Cortinovis, M. Noris, G. Remuzzi. - In: TRANSPLANT INTERNATIONAL. - ISSN 0934-0874. - 26:9(2013 Sep), pp. 867-878.

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