Pancreatic islet surface engineering with a starPEG-chondroitin sulfate nanocoating

Abstract

Islet transplantation is one of the most promising therapeutic options that could restore euglycaemia in type 1 diabetic individuals. The currently implemented alginate microsphere islet encapsulation approach has led to positive outcomes in improving intraportal islet delivery in rodents. However, results obtained from human clinical trials remain disappointing. The less than satisfactory clinical outcome is mainly attributable to the increased size of the encapsulated islet and alginate-elicited host immune responses. In order to achieve islet encapsulation without significant alteration of the islet size, we designed and prepared a chondroitin sulfate (CS)-incorporated starPEG nanocoating (CS-PEG) that conjugates covalently to the pancreatic islet cell surface amine groups via pseudo-orthogonal chemistry for islet surface engineering. CS-PEG surface engineering incurred minimal alteration of the islet volume. Enhanced in situ revascularization, which is protective against extracellular matrix disruption, was also observed from CS-PEG islets in addition to robust islet viability and uncompromised insulin secretory ability. More importantly, CS-PEG surface engineering reduced blood coagulation while facilitating islet cell survival under pro-inflammatory conditions. Given that host immune rejection and an instant blood-mediated inflammatory reaction (IBMIR) are the primary factors detrimental to islet engraftment and survival, often resulting in rapid cell loss and graft failure, CS-PEG surface engineering provides an “easy-to-adopt” approach for cell surface engineering that could potentially improve the clinical efficacy of islet transplantation and other types of cell therapies.