Application of AN69 hydrogel to islet encapsulation. Evaluation in streptozotocin-induced diabetic rat model

The polymer AN69 (polyacrylonitrile-sodium methallylsulfonate) is a reference in biocompatibility in the field of hemodialysis. Its use for the encapsulation of living cells has been already described, but this study is the first description of AN69 hydrogel-encapsulated islet isograft in streptozotocin (STZ) diabetic rats. The aim of this work is to evaluate the biocompatibility of the AN69 hydrogel by comparison of the efficacy of free versus encapsulated islets transplanted to balance diabetes. Pancreatic islets are isolated from adult male Lewis rats by a standard collagenase digestion and purified on Ficoll density gradients. The AN69 hollow fiber is obtained by coextrusion of an 8% AN69 collodion. The hollow fiber is filled with islets suspended in agarose at the final concentration of 10,000 islets/ml, closed with surgical clips and implanted. The recipients are rendered diabetic by intravenous injection of STZ. The experimental design includes 4 groups of 8 rats: group 1: control, group 2: diabetic rats intraperitoneally implanted with 6000 free islets, group 3: diabetic rats intraperitoneally implanted with 9000 encapsulated islets, group 4: diabetic control. Weight and fasting glycemia are evaluated twice a week, diuresis once a week. After free islet implantation, rat survival is improved with glycemia below 250 mg/dl during 22 days. Compared to group 2, the status of group 3 is better, with a glycemia below 250 mg/dl during at least 70 days. This tends to demonstrate the biocompatibility of AN69 and is the first step of the validation of the use of AN69 for living cell encapsulation.