title: Co-transplantation of autologous MSCs delays islet allograft rejection and generates a local immunoprivileged site.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors: Nephrology Division, Boston Children's Hospital, Harvard Medical School, Enders Building 5th Floor Room EN511, 300 Longwood Ave, Boston, MA, USA.|Transplant Medicine, Ospedale San Raffaele, Milan, Italy.
authors: Moufida
authors: M
authors: Ben Nasr
authors: Nephrology Division, Boston Children's Hospital, Harvard Medical School, Enders Building 5th Floor Room EN511, 300 Longwood Ave, Boston, MA, USA.|Transplant Medicine, Ospedale San Raffaele, Milan, Italy.
authors: Andrea
authors: A
authors: Vergani
authors: Transplantation Unit, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA.
authors: James
authors: J
authors: Avruch
authors: Transplantation Unit, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA.
authors: Liye
authors: L
authors: Liu
authors: Renal Division, Brigham and Women's Hospital, Harvard Institute of Medicine, HIM510, Harvard Medical School, Boston, MA, 02115, USA.
authors: Eirini
authors: E
authors: Kefaloyianni
authors: Nephrology Division, Boston Children's Hospital, Harvard Medical School, Enders Building 5th Floor Room EN511, 300 Longwood Ave, Boston, MA, USA.|Transplant Medicine, Ospedale San Raffaele, Milan, Italy.
authors: Francesca
authors: F
authors: D'Addio
authors: Nephrology Division, Boston Children's Hospital, Harvard Medical School, Enders Building 5th Floor Room EN511, 300 Longwood Ave, Boston, MA, USA.
authors: Sara
authors: S
authors: Tezza
authors: Pathology and Laboratory Medicine, University of Parma, Parma, Italy.
authors: Domenico
authors: D
authors: Corradi
authors: Nephrology Division, Boston Children's Hospital, Harvard Medical School, Enders Building 5th Floor Room EN511, 300 Longwood Ave, Boston, MA, USA.
authors: Roberto
authors: R
authors: Bassi
authors: Transplant Medicine, Ospedale San Raffaele, Milan, Italy.
authors: Alessandro
authors: A
authors: Valderrama-Vasquez
authors: Transplant Medicine, Ospedale San Raffaele, Milan, Italy.
authors: Vera
authors: V
authors: Usuelli
authors: Transplantation Unit, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA.
authors: James
authors: J
authors: Kim
authors: Nephrology Division, Transplantation Research Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors: Jamil
authors: J
authors: Azzi
authors: Department of Medicine, Al-Azhar University, Cairo, Egypt.
authors: Basset
authors: B
authors: El Essawy
authors: Transplantation Unit, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA.
authors: James
authors: J
authors: Markmann
authors: Nephrology Division, Transplantation Research Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors: Reza
authors: R
authors: Abdi
authors: Nephrology Division, Boston Children's Hospital, Harvard Medical School, Enders Building 5th Floor Room EN511, 300 Longwood Ave, Boston, MA, USA. paolo.fiorina@childrens.harvard.edu.|Transplant Medicine, Ospedale San Raffaele, Milan, Italy. paolo.fiorina@childrens.harvard.edu.
authors: Paolo
authors: P
authors: Fiorina
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology; D016026:Bone Marrow Transplantation / Q000379:methods; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006085:Graft Survival; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D007959:Lymphocyte Culture Test, Mixed; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000276:immunology / Q000648:ultrastructure; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000166:cytology; D058504:Th17 Cells / Q000276:immunology
chemical_list: D016207:Cytokines
keywords: Immunoprivileged site; Immunoregulation; Islet transplantation; Mesenchymal stem cells