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Presenter: S., Veriter, Brussels, Belgium
Authors: S. Veriter, N. Aouassar, P.Y. Adnet, B. Jordan, B. Gallez, P. Gianello, D. Dufrane
Oxygenation of subcutaneous bioartificial pancreas: effect of diabetic state and islet encapsulation
S. Veriter1, N. Aouassar1, P.Y. Adnet1, B. Jordan2, B. Gallez2, P. Gianello1, D. Dufrane1
1 Université catholique de Louvain, Laboratory of Experimental Surgery, Brussels, Belgium; 2 Université catholique de Louvain, Biomedical Magnetic Resonance Unit, Brussels, Belgium
Objective: Although high-mannuronic alginate provides a sufficient oxygenation (5% O2) for encapsulated islets survival after subcutaneous transplantation in non-diabetic rats, ~30% of islets are lost during the first week post-transplantation. Micro/macrovascular lesions due to diabetes and oxygen consumption by encapsulated islets could explain the early cellular death. Therefore, we investigated, both in vitro and in vivo, the impact of diabetes and encapsulated islets on implant oxygenation and neovascularization.
Methods: Non-diabetic and streptozotocin-diabetic rats were transplanted with high-mannuronic empty implants (n=15 and 11, respectively) or encapsulated porcine islets (n=8 and 8, respectively). Oxygenation was weekly measured in vivo by Electonic Paramagnetic Resonance (EPR). Four weeks after transplantation, neoangiogenesis surrounding the implant, vascular density and the number of cells expressing Vascular Endothelial Growth Factor (VEGF) were assessed by histomorphometry. The impact of hyperglycemia and islet encapsulation on oxygen consumption by islets was assessed in vivo by EPR. The impact of hypoxia and hyperglycemia, on the islet capacity to secrete VEGF (quantified by ELISA) was studied by incubation at 3 and 21% O2 at 5 and 25 mM glucose.
Results: Hyperglycemia induced a significant decrease of implant oxygenation (~3% O2), accentuated with the presence of islets (~2% O2) in comparison to ~5% O2 for empty implants grafted in non-diabetic rats (p<0.05). The islets oxygen consumption (in vitro) was not affected by the hyperglycemia and encapsulation in alginate. The connective tissue surrounding encapsulated islets (in non-/diabetic rats) expressed a significant higher level of VEGF than empty capsules grafted in non-diabetic rats (148.6±8.5 vs. 34.4±3.7 VEGF-expressing cells/0.16mm²; p<0.05). This was related to a 1.4 times higher level of VEGF secretion by islets in normoglycemia/normoxia in comparison to hyperglycemic/hypoxic groups (p<0.05).
Conclusion: Diabetes and oxygen consumption by encapsulated islets induce a decrease of implant’s oxygenation associated with an increased VEGF expression.
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