In vivo vascularization and islet function in a microwell device for pancreatic islet transplantation

Abstract

Islet encapsulation in membrane-based devices could allow for transplantation of donor islet tissue in the absence of immunosuppression. To achieve long-term survival of islets, the device should allow rapid exchange of essential nutrients and be vascularized to guarantee continued support of islet function. Recently, we have proposed a membrane-based macroencapsulation device consisting of a microwell membrane for islet separation covered by a micropatterned membrane lid. The device can prevent islet aggregation and support functional islet survival<i>in vitro</i>. Here, based on previous modeling studies, we develop an improved device with smaller microwell dimensions, decreased spacing between the microwells and reduced membrane thickness and investigate its performance<i>in vitro</i>and<i>in vivo</i>. This improved device allows for encapsulating higher islet numbers without islet aggregation and by applying an<i>in vivo</i>imaging system we demonstrate very good perfusion of the device when implanted intraperitoneally in mice. Besides, when it is implanted subcutaneously in mice, islet viability is maintained and a vascular network in close proximity to the device is developed. All these important findings demonstrate the potential of this device for islet transplantation.