Mesenchymal stromal cells and kidney transplantation: pretransplant infusion protects from graft dysfunction while fostering immunoregulation
| Autor: | Martino Introna, Federica Casiraghi, Marina Noris, Norberto Perico, Giuseppe Remuzzi, Regiane Aparecida Cavinato, Marta Todeschini, Paola Cassis, Eliana Gotti, Paola Rizzo, Monica Cortinovis, Chiara Capelli, Alessandro Rambaldi |
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| Rok vydání: | 2013 |
| Předmět: |
Adult
Graft Rejection Male medicine.medical_specialty Basiliximab Recombinant Fusion Proteins Population Urology Mesenchymal Stem Cell Transplantation T-Lymphocytes Regulatory Clinical Protocols Transplantation Immunology medicine Humans education Kidney transplantation Antilymphocyte Serum Transplantation education.field_of_study Kidney business.industry Mesenchymal stem cell Antibodies Monoclonal FOXP3 medicine.disease Kidney Transplantation medicine.anatomical_structure Immunology Kidney Failure Chronic Female business Immunosuppressive Agents CD8 medicine.drug |
| Zdroj: | Transplant International. 26:867-878 |
| ISSN: | 0934-0874 0075-2479 |
| DOI: | 10.1111/tri.12132 |
| Popis: | 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). |
| Databáze: | OpenAIRE |
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