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Presenter: Alice A., Tomei, Miami, United States
Authors: Alice A. Tomei1,2, Mejdi Najjar1,2, Vita Manzoli1,2, Chiara Villa1,2, Mikael M. Martino1,2, Ruth D. Molano1,2, Antonello Pileggi1,2, Luca Inverardi1,2, Camillo Ricordi1,2, Jeffrey A. Hubbell1,2
Alice A. Tomei1,2, Mejdi Najjar1,2, Vita Manzoli1,2, Chiara Villa1,2, Mikael M. Martino1,2, Ruth D. Molano1,2, Antonello Pileggi1,2, Luca Inverardi1,2, Camillo Ricordi1,2, Jeffrey A. Hubbell1,2
1Diabetes Research Institute, University of Miami, Miller School of Medicine, Miami, FL, United States; 2Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland
We have engineered the SC and the EFP sites for islet transplantation to promote angiogenesis with the goal of decreasing early graft loss and improving islet engraftment. We have utilized novel fibrin matrices as biodegradable scaffolds for local controlled release of pro-angiogenic growth factors through proteolitically cleavable recombinant fibronectin proteins that can bind both cells involved in tissue re-vascularization and growth factors. We chose to use degradable matrices to prevent fibrotic reactions that have been observed for permanent scaffolds. We show that in the SC site, 60% of mice transplanted with a marginal mass of 1,000 IEQ syngeneic islets within engineered matrices reverse diabetes at 40 days post-transplant (average reversal time 38 days, n=5) versus 20% of mice transplanted with islets alone after 100 days (undefined average reversal time, n=5). In the SC site, islet engraftment in engineered matrices is associated with neogenesis of blood vascular networks by day 7 and full vascularization by day 21. In the EFP site, 60% of mice transplanted with a marginal mass of 250 IEQ syngeneic islets within engineered matrices (average reversal time 24 days, n=10) and 10% of mice transplanted with islets alone reverse diabetes after 40 days (average reversal time: 85.5, n=8). In EFP grafts, islet density in grafts retrieved after 100 days and density of blood vessels is higher in the engineered matrices group (p<0.05). Also, proportion of beta and alpha cells in grafted islets is comparable to the one found in native pancreas. Our findings suggest that by promoting early re-vascularization of islet grafts we can promote engraftment and long-term function in the SC and EFP sites, which are clinically relevant sites.
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