2013 - CTS 2013 Congress


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Oral Communications 2

6.3 - Transplantation of pancreatic islets in the omental pouch using a resorbable plasma-thrombin gel: preliminary results in rodents and nonhuman primates

Presenter: Antonello , Pileggi , Miami, United States
Authors: Dora Berman1,2,3,4, Antonello Pileggi1,2,3,4, R. Damaris Molano1,2,3,4, Carmen Fotino1,2,3,4, Norman M. Kenyon1,2,3,4, Norma S. Kenyon1,2,3,4, Camillo Ricordi1,2,3,4

Transplantation of pancreatic islets in the omental pouch using a resorbable plasma-thrombin gel: preliminary results in rodents and nonhuman primates

Dora Berman1,2,3,4, Antonello Pileggi1,2,3,4, R. Damaris Molano1,2,3,4, Carmen Fotino1,2,3,4, Norman M. Kenyon1,2,3,4, Norma S. Kenyon1,2,3,4, Camillo Ricordi1,2,3,4

1Diabetes Research Institute, University of Miami, Miami, FL, United States; 2Surgery, University of Miami Miller School of Medicine, Miami, FL, United States; 3Surgery, Microbiology and Immunology, Biomedical Engineering, University of Miami, Miami, FL USA, FL, United States; 4Medicine, University of Miami Miller School of Medicine, Miami, FL, United States

Transplantation of pancreatic islets is a viable therapeutic option for the treatment of unstable diabetes.  Currently, islets are transplanted into the portal venous system through their embolization into the liver sinusoids resulting in loss of a substantial islet mass to inflammation and hypoxia.  The need for developing alternative, extra-hepatic implantation sites for islets has been recognized. Implantation of islets into omental pouches is appealing because the omentum is well vascularized and has portal blood drainage.

We tested the function of islets transplanted in the omental pouch site in a plasma clot induced with the addition of clinical grade recombinant thrombin.  Human islets transplanted in the omental pouch of streptozotocin (STZ)-induced diabetic athymic mice reverted diabetes, maintained sustained normoglycemia and normal clearance during glucose tolerance test.  Resection of the graft-bearing omental pouches resulted in prompt return to hyperglycemia.  Histopathology of the explanted grafts displayed well-preserved islets with insulin and glucagon signals. 
 
We also performed a pilot allogeneic islet transplant in a STZ-induced diabetic cynomolgus monkey under thymoglobin (10mg/kg IV on days -1, 0, 2 and 4), anti-CTLA4Ig (Belatacept; 20mg/kg IV on days 0, 4, 14, 28, 56, 75 and monthly thereafter at 10mg/kg) and Sirolimus (from day 2 targeting trough levels of 8-12ng/ml).  After transplantation, basal c-peptide levels became detectable paralleling reduction in insulin requirements over time.  Preliminary histopathological assessment of the graft 49-days after transplant showed well preserved islets with immunoreactivity for endocrine markers.
 
Our preliminary data suggest that the use of a clinical-grade resorbable plasma-thrombin gel in an omental pouch allows engraftment of transplanted islets. 


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