Selection of Implantation Sites for Transplantation of Encapsulated Pancreatic Islets

Abstract

Pancreatic islet transplantation has been validated as a valuable therapy for type 1 diabetes mellitus patients with exhausted insulin treatment. However, this therapy remains limited by the shortage of donor and the requirement of lifelong immunosuppression. Islet encapsulation, as an available bioartificial pancreas (BAP), represents a promising approach to enable protecting islet grafts without or with minimal immunosuppression and possibly expanding the donor pool. To develop a clinically implantable BAP, some key aspects need to be taken into account: encapsulation material, capsule design, and implant site. Among them, the implant site exerts an important influence on the engraftment, stability, and biocompatibility of implanted BAP. Currently, an optimal site for encapsulated islet transplantation may include sufficient capacity to host large graft volumes, portal drainage, ease of access using safe and reproducible procedure, adequate blood/oxygen supply, minimal immune/inflammatory reaction, pliable for noninvasive imaging and biopsy, and potential of local microenvironment manipulation or bioengineering. Varying degrees of success have been confirmed with the utilization of liver or extrahepatic sites in an experimental or preclinical setting. However, the ideal implant site remains to be further engineered or selected for the widespread application of encapsulated islet transplantation.