Metabolômica: Acesso Aberto

Poloxamer 188 as a Supplement to Barium Cross-Linked Ultra-High Viscosity Alginate for Immunoisolation of Transplanted Islet Cells

Abstract

Mettler E, Zimmermann U, Hansen T, Ehrhart F, Zimmermann H and Weber MM

Transplantation of Langerhans islets is a potential cure for diabetes mellitus. The main problem for routine clinical use remains the prevention of rejection without drastic side effects. Immuno-isolation is an experimental strategy to prevent graft rejection by separating the transplanted cells from the host immune system using a barrier device. The aim of the current study was to improve the physical features of encapsulated islets in a barium cross-linked ultra-high viscosity alginate by adding Poloxamer 188 (P188). Empty alginate capsules, and especially encapsulated islets, could be easily generated using UHV-P188 alginate because of its anti-foaming properties. Diabetic mice were used for evaluation of biocompatibility and graft function. Biocompatibility testing with empty capsules showed no inflammatory reaction or fibrotic overgrowth. The capsules remained intact in the intraperitoneal and intramuscular implant sites over a period of 4 weeks. Transplantation of encapsulated islets, however, led to a strong systemic inflammatory response with fibrotic overgrowth of the islet-containing capsules but no graft failure. This finding likely reflected the complementactivating property of P188. Our results clearly showed that the complex interaction of additives, xenogeneic tissue, and alginate with the host immune system could not be predicted by the behavior of the individual components. Furthermore, the mouse model described herein was an excellent tool to evaluate the physico-chemical properties and the in vivo biocompatibility and functionality of various additives. Our results will improve the biomaterials used for alginate microbeads in a clinical setting in the future.