In vitro and in vivo performance of porcine islets encapsulated in interfacially photopolymerized poly(ethylene glycol) diacrylate membranes.

摘要

The usefulness of interfacial photopolymerization of poly(ethylene glycol) (PEG) diacrylate at a variety of concentrations and molecular weights to form hydrogel membranes for encapsulating porcine islets of Langerhans was investigated. The results from this study show in vitro and in vivo function of PEG-encapsulated porcine islets and the ability of PEG membranes to prevent immune rejection in a discordant xenograft model. Encapsulated islets demonstrated an average viability of 85% during the first week after encapsulation, slightly but significantly lower than unencapsulated controls. Encapsulated porcine islets were shown to be glucose responsive using static glucose stimulation and perifusion assays. Higher rates of insulin release were observed for porcine islets encapsulated in lower concentrations of PEG diacrylate (10-13%), not significantly reduced relative to unencapsulated controls, than were observed in islets encapsulated in higher concentrations (25%) of PEG diacrylate. Perifusion results showed biphasic insulin release from encapsulated islets in response to glucose stimulation. Streptozotocin-induced diabetic athymic mice maintained normoglycemia for up to 110 days after the implantation of 5,000-8,000 encapsulated porcine islet equivalents into the peritoneal cavity. Normoglycemia was also confirmed in these animals using glucose tolerance tests. PEG diacrylate-encapsulated porcine islets were shown to be viable and contain insulin after 30 days in the peritoneal cavity of Sprague-Dawley rats, a discordant xenograft model. From these studies, we conclude that PEG diacrylate encapsulation of porcine islets by interfacial photopolymerization shows promise for use as a method of xenoprotection toward a bioartificial endocrine pancreas.