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Presenter: A., Sterkers, Lille, France
Authors: F. Pattou, A Sterkers
Bench to bedside translation of intramuscular islet autotransplantation
F. Pattou, A Sterkers
Lille University Hospital, INSERM UMR 859, Lille, France
Background: Intra muscular transplantation (IMT) offers attractive prospects for islet transplantation. The clinical relevance of this non invasive alternative to the intraportal route remains is not clearly established. We developed in the minipig a simple and reproducible technique for islet IMT and tested its clinical relevance for islet autotransplantation.
Methods: Islets were isolated from adult minipigs (n=25) with standard automated technique following distal pancreatectomy. Standardized autologous islet grafts were implanted in the thigh gracilius muscle. Transplant sites were explanted and analyzed by immunochemistry for cell composition (insulin, glucagon) and vascularization (vWF). A similar technique was applied in two patients who underwent islet autotransplantation in the left forearm after an extended pancreatectomy for benign tumors.
Results: In the minipig, immunochemistry confirmed the presence of alpha and beta cells up to 6 months after transplantation. Islets revascularization increased betwen day 15 and day 30 and was correlated with islet survival. Graft function was documented by acute insulin response (AIR) after completion of the pancreatectomy at one month in 2 animals. Clinical islet IMT was uneventfull in both cases. Ectopic insulin secretion could be documented by AIR with or without forearm vascular exclusion, and represented 53% and 22% of the overall systemic insulin secretion, respectively. Islet survival was confirmed by scintigraphy with radiolabeled GLP1 analogs after one year in our first patient.
Conclusion: These results provided unequivocal proof of prolonged survival, revascularization and function of pancreatic islets after IMT and confirmed the clinical relevance of this strategy for islet autotransplantation.
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