251 Effect of GCSF and GLP1 Agonist on Long-Term Human Islet Allograft Survival
Monday November 16, 2015 from 11:00 to 12:30
Plenary Room 1

Camillo Ricordi, United States

Professor and Director

Diabetes Research Institute, Department of Surgery, Division of Cellular Transplantation

University of Miami


Effect of GCSF and GLP1 Agonist on Long-Term Human Islet Allograft Survival

Camillo Ricordi 1, Paolo Serafini1, Alessia Zoso1, Giacomo Lanzoni1, Eduardo M Peixoto1, Muyesser S Arslan1, Rodolfo Alejandro1, Luca Inverardi1.

1Diabetes Research Institute, University of Miami, Miami, FL, United States

Subjects with Type 1 Diabetes (T1D) could benefit from treatments that support prolonged survival of beta cells. Filgrastim is a granulocyte colony stimulating factor (GCSF) analog used to stimulate neutrophils in neutropenic islet transplant recipients. GCSF induces myeloid derived suppressor cells (MDSCs), potent immunosuppressive cells. We observed that the induction of MDSCs delays the occurrence of Type 1 Diabetes in NOD mice. Filgrastim could delay the rejection of transplanted islet cells. We retrospectively analyzed the duration of islet graft survival in our cohort of islet transplant recipients (n=44). We compared graft survival in filgrastim treated (n=16) versus untreated (n=28) transplant recipients. We observed that 4500 days after transplant, graft function was present in >60% of filgrastim treated patients, and in <30% of untreated patients. Exenatide is a Glucagon like Peptide1 (GLP1) agonist that regulates glucose metabolism by enhancing insulin secretion by beta cells. GLP1 and Exenatide reduce beta cell apoptosis, stimulate beta cell proliferation and neogenesis. Graft survival was prolonged in islet recipients treated with exenatide (n=31; p<0.05) with the best results observed in subjects who received both GCSF and Exenatide (n=7; p<0.05). Strikingly, graft survival exceeded 4 years in 100% of islet transplant recipients treated with both drugs (see Figure).  Additional prospective clinical trials are planned to determine the possible beneficial effect of the combination of GCSF and GLP1 analogs in both islet transplantation and reversal of autoimmunity following T1D onset (intervention trials).  

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