Transplantation of Islet-Containing microcapsules modified with constitutional isomers of sulfated alginate in diabetic mice to mitigate fibrosis for Long-term glycemic control

Abstract

• We showed that different stereochemistries of a material can influence its biocompatibility. • Regioselectivity of sulfate groups significantly affect the biocompatibility of the alginate. • Sulfated alginate was found as a more biocompatible material than neat alginate. • Sulfated alginate is an appropriate coating candidate to use in islet microencapsulation. Type 1 diabetes, an autoimmune disease, is increasing in prevalence worldwide. Pancreatic islet encapsulation by biocompatible alginate hydrogels may be a promising cell-based therapy approach to control blood glucose levels in patients with type 1 diabetes. However, a substantial obstacle to this approach is the immune system’s reaction to the presence of a foreign body and fibrosis formation. In this study, we used three methods to synthesize three different constitutional isomers of sulfated alginate by sulfation of uronic acid residues of alginate. Next, we evaluated the effects of the different stereochemistries of these isomers on alginate biocompatibility. In addition, we assessed the immune system response to these isomers. The calcium sulfated alginate microcapsules were subcutaneously implanted into male Wistar rats. After 14 days, the samples were evaluated by histological and immunofluorescent analyses. The results showed considerable variations in biocompatibility of the islet-free microcapsules that contained the different stereochemistries. Next, we chose the best samples that mitigated fibrosis and used them as the third layer of three-layer microcapsules that contained pancreatic islets. These microcapsules were subsequently transplanted into the omental pouches of diabetic mice. Interestingly, the mice had reduced blood glucose levels for more than six weeks. Both the intraperitoneal glucose tolerance test (IP-GTT) and C-peptide analyses showed correct function of the transplanted islets in these diabetic mice at four and six weeks after transplantation, respectively. There was a significant reduction in collagen content around the transplanted microcapsules in both the method 1 (M1) and method 3 (M3) coated groups (sulfated alginates) compared with the alginate group.