Cell-mimic polymersome-shielded islets for long-term immune protection of neonatal porcine islet-like cell clusters

Abstract

Although islet cell transplantation has emerged as a promising treatment for type 1 diabetes, it remains an unmet clinical application due to the need for immunosuppression to prevent islet elimination and autoimmunity. To solve these problems, we developed novel nanoencapsulation of neonatal porcine islet-like cell clusters (NPCCs) with cell-mimic polymersomes (PSomes) based on PEG-b-PLA (poly(ethylene glycol)-b-poly(dl-lactic acid)). To accomplish this, we first formulated NHS-, NH2-, COOH-, and m(methoxy)-PSomes. This coating utilizes interactions involving NPCC surfaces and PSomes that have covalent bonds, electrostatic interactions, and hydrogen bonds. We extended the range of applicability by comparing the binding affinity of electrostatic attraction and hydrogen bonding, as well as covalent bonds. Our protocol can be used as an efficient hydrogen bonding method because it reduces cell membrane damage as well as the use of covalent bonding methods. We verified the selective permeability of NHS-, NH2-, COOH-, and m-PSome-shielded NPCCs. Furthermore, we showed that a novel nanoencapsulation did not affect insulin secretion from NPCCs. This study offers engineering advances in islet encapsulation technologies to be used for cell-based transplantation therapies.