Mesenchymal stem cells prevent acute rejection and prolong graft function in pancreatic islet transplantation.
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.
Longoni
Biancamaria
B
Department of Oncology, Transplantation and Advanced Technology in Medicine, University of Pisa, Pisa, Italy. biancam@dfb.unipi.it
Szilagyi
Erzsebet
E
Quaranta
Paola
P
Paoli
Giacomo Timoteo
GT
Tripodi
Sergio
S
Urbani
Serena
S
Mazzanti
Benedetta
B
Rossi
Benedetta
B
Fanci
Rosa
R
Demontis
Gian Carlo
GC
Marzola
Pasquina
P
Saccardi
Riccardo
R
Cintorino
Marcella
M
Mosca
Franco
F
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