title: Mesenchymal stromal cells and kidney transplantation: pretransplant infusion protects from graft dysfunction while fostering immunoregulation.
abstract: 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).
authors.affiliation: Department of Immunology and Transplantation, Azienda Ospedaliera - IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Bergamo, Italy.
authors.forename: Norberto
authors.initials: N
authors.lastname: Perico
authors.forename: Federica
authors.initials: F
authors.lastname: Casiraghi
authors.forename: Eliana
authors.initials: E
authors.lastname: Gotti
authors.forename: Martino
authors.initials: M
authors.lastname: Introna
authors.forename: Marta
authors.initials: M
authors.lastname: Todeschini
authors.forename: Regiane Aparecida
authors.initials: RA
authors.lastname: Cavinato
authors.forename: Chiara
authors.initials: C
authors.lastname: Capelli
authors.forename: Alessandro
authors.initials: A
authors.lastname: Rambaldi
authors.forename: Paola
authors.initials: P
authors.lastname: Cassis
authors.forename: Paola
authors.initials: P
authors.lastname: Rizzo
authors.forename: Monica
authors.initials: M
authors.lastname: Cortinovis
authors.forename: Marina
authors.initials: M
authors.lastname: Noris
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Remuzzi
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000009:adverse effects; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D000077552:Basiliximab; D002985:Clinical Protocols; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects; D007676:Kidney Failure, Chronic / Q000601:surgery; D016030:Kidney Transplantation / Q000379:methods*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D011993:Recombinant Fusion Proteins / Q000009:adverse effects; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D014181:Transplantation Immunology
chemical_list: D000911:Antibodies, Monoclonal; D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D011993:Recombinant Fusion Proteins; D000077552:Basiliximab
keywords: immunomodulation; living-related kidney transplantation; mesenchymal stromal cells; pretransplant cell infusion