title: Mesenchymal stem cells prevent acute rejection and prolong graft function in pancreatic islet transplantation.
abstract: BACKGROUND
  Pancreatic islet transplantation is a promising cell-based therapy for type 1 diabetes (insulin-dependent diabetes mellitus), a disease triggered by the immune response against autoantigens of beta-cells. However, the recurrence of immune response after transplantation and the diabetogenic and growth-stunting side effects of immunosuppressants are major challenges to the application of islet transplantation. Mesenchymal stem cells (MSCs) have recently been reported to modulate the immune response in allogeneic transplantation.
  
  
  METHODS
  The ability of MSCs, either syngeneic or allogeneic to recipients, to prevent acute rejection and improve glycemic control was investigated in rats with diabetes given a marginal mass of pancreatic islets through the portal vein.
  
  
  RESULTS
  Reduced glucose levels and low-grade rejections were observed up to 15 days after transplantation upon triple-dose administration of MSCs, indicating that MSCs prolong graft function by preventing acute rejection. The efficacy of MSCs was associated with a reduction of pro-inflammatory cytokines and was independent of the administration route. Efficacy was similar for MSCs whether syngeneic or allogeneic to recipients and comparable to that of immunosuppressive therapy.
  
  
  CONCLUSIONS
  The results show that MSCs modulate the immune response through a down-regulation of pro-inflammatory cytokines, suggesting that MSCs may prevent acute rejection and improve graft function in portal vein pancreatic islet transplantation.
authors.affiliation: Department of Oncology, Transplantation and Advanced Technology in Medicine, University of Pisa, Pisa, Italy. biancam@dfb.unipi.it
authors.forename: Biancamaria
authors.initials: B
authors.lastname: Longoni
authors.forename: Erzsebet
authors.initials: E
authors.lastname: Szilagyi
authors.forename: Paola
authors.initials: P
authors.lastname: Quaranta
authors.forename: Giacomo Timoteo
authors.initials: GT
authors.lastname: Paoli
authors.forename: Sergio
authors.initials: S
authors.lastname: Tripodi
authors.forename: Serena
authors.initials: S
authors.lastname: Urbani
authors.forename: Benedetta
authors.initials: B
authors.lastname: Mazzanti
authors.forename: Benedetta
authors.initials: B
authors.lastname: Rossi
authors.forename: Rosa
authors.initials: R
authors.lastname: Fanci
authors.forename: Gian Carlo
authors.initials: GC
authors.lastname: Demontis
authors.forename: Pasquina
authors.initials: P
authors.lastname: Marzola
authors.forename: Riccardo
authors.initials: R
authors.lastname: Saccardi
authors.forename: Marcella
authors.initials: M
authors.lastname: Cintorino
authors.forename: Franco
authors.initials: F
authors.lastname: Mosca
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000628:therapy*; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D007150:Immunohistochemistry; D007165:Immunosuppression Therapy; D050417:Insulin-Secreting Cells / Q000276:immunology; D007515:Islets of Langerhans / Q000276:immunology; D016381:Islets of Langerhans Transplantation / Q000276:immunology / Q000379:methods*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley