Aims: Mesenchymal stem cells (MSCs) are multipotent cells with immunomodulatory properties. We tested the ability of MSCs to delay islet allograft rejection. Methods: Mesenchymal stem cells were generated in vitro from C57BL/6 and BALB/c mice bone marrow, and their immunomodulatory properties were tested in vitro. We then tested the effect of a local or systemic administration of heterologous and autologous MSCs on graft survival in a fully allogeneic model of islet transplantation (BALB/c islets into C57BL/6 mice). Results: In vitro, autologous, but not heterologous, MSCs abrogated immune cell proliferation in response to alloantigens and skewed the immune response toward a Th2 profile. A single dose of autologous MSCs co-transplanted under the kidney capsule with allogeneic islets delayed islet rejection, reduced graft infiltration, and induced long-term graft function in 30 % of recipients. Based on ex vivo analysis of recipient splenocytes, the use of autologous MSCs did not appear to have any systemic effect on the immune response toward graft alloantigens. The systemic injection of autologous MSCs or the local injection of heterologous MSCs failed to delay islet graft rejection. Conclusion: Autologous, but not heterologous, MSCs showed multiple immunoregulatory properties in vitro and delayed allograft rejection in vivo when co-transplanted with islets; however, they failed to prevent rejection when injected systemically. Autologous MSCs thus appear to produce a local immunoprivileged site, which promotes graft survival.
Co-transplantation of autologous MSCs delays islet allograft rejection and generates a local immunoprivileged site / M. Ben Nasr, A. Vergani, J. Avruch, L. Liu, E. Kefaloyianni, F. D’Addio, S. Tezza, D. Corradi, R. Bassi, A. Valderrama Vasquez, V. Usuelli, J. Kim, J. Azzi, B. El Essawy, J. Markmann, R. Abdi, P. Fiorina. - In: ACTA DIABETOLOGICA. - ISSN 0940-5429. - 52:5(2015), pp. 917-927.
|Titolo:||Co-transplantation of autologous MSCs delays islet allograft rejection and generates a local immunoprivileged site|
FIORINA, PAOLO (Ultimo) (Corresponding)
|Parole Chiave:||Immunoprivileged site; Immunoregulation; Islet transplantation; Mesenchymal stem cells; Animals; Bone Marrow Cells; Bone Marrow Transplantation; Cell Proliferation; Cytokines; Graft Rejection; Graft Survival; Islets of Langerhans Transplantation; Lymphocyte Culture Test, Mixed; Mesenchymal Stem Cell Transplantation; Mesenchymal Stromal Cells; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Spleen; Th17 Cells; Internal Medicine; Endocrinology, Diabetes and Metabolism; Endocrinology|
|Settore Scientifico Disciplinare:||Settore MED/13 - Endocrinologia|
|Data di pubblicazione:||2015|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1007/s00592-015-0735-y|
|Appare nelle tipologie:||01 - Articolo su periodico|