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

Mettler E,Zimmermann U

doi:10.4172/2153-0769.1000157

Abstract

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.

Highlights

We have been investigating rat pancreatic xenografts as a potential source of functional islet tissue for transplantation using a mouse model
The goal of this work was to develop a therapeutic strategy to overcome the shortage of donor organs for the treatment of diabetes mellitus
The retrieved empty alginate droplets did not exhibit any cellular overgrowth on their surfaces (Figure 2)

Summary

Introduction

We have been investigating rat pancreatic xenografts as a potential source of functional islet tissue for transplantation using a mouse model. To prevent strong humoral and cellular immune responses to the xenografts, we tested alginate microcapsules as an immunoisolation device. According to our previously published results [2], the use of ultra-high viscosity (UHV) alginate for microencapsulation provided long-term functional rat and human islets after intraperitoneal xenotransplantation into immunocompetent diabetic mice, without the need for immunosuppression. Depending on the nature of the cross-linking cation, the length of the polymeric chains, the mannuronic acid:guluronic acid (M:G) ratio, and the percentage of block structures, hydrogels of varying mechanical strength, elasticity, and swelling characteristics can be produced [4]. The M:G ratio, length of polymeric chains, and ratio of homologous to heterologous chains must be carefully tuned to optimize the microcapsules [6]

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