Prebiotic inulin nanocoating for pancreatic islet surface engineering

Abstract

Pancreatic islet surface engineering has been proposed as an “easy-to-adopt” approach to enhance post-transplantation islet engraftment for treatment against diabetes. Inulin is an FDA-approved dietary prebiotic with reported anti-diabetic, anti-inflammatory, anti-hypoxic and pro-angiogenic properties. We therefore assessed whether inulin would be a viable option for islet surface engineering. Inulin was oxidized to generate inulin-CHO, which would bind to the cell membrane via covalent bond formation between –CHO and –NH₂ across the islet cell membrane. In vitro assessments demonstrated enhanced islet viability and better glucose-induced insulin secretion from inulin-coated (5 mg mL⁻¹) islets, which was accompanied by enhanced revascularization, shown as significantly enhanced tube formation and branching of islet endothelial MS1 cells following co-culture with inulin-coated islets. Reduction of cytokine-induced cell death was also observed from inulin-coated islets following exposure to pro-inflammatory cytokine LPS. LPS-induced ROS production was significantly dampened by 44% in inulin-coated islets when compared to controls. RNA-seq analysis of inulin-coated and control islets identified expression alterations of genes involved in islet function, vascular formation and immune regulation, supporting the positive impact of inulin on islet preservation. In vivo examination using streptozotocin (STZ)-induced hyperglycemic mice further showed moderately better maintained plasma glucose levels in mice received transplantation of inulin-coated islets, attributable to ameliorated CD45⁺ immune cell infiltration and improved in vivo graft vascularization. We therefore propose islet surface engineering with inulin as safe and beneficial, and further assessment is required to verify its applicability in clinical islet transplantation.