Revascularization of Transplanted Pancreatic Islets and Role of the Transplantation Site

Abstract

Since the initial reporting of the successful reversal of hyperglycemia through the transplantation of pancreatic islets, significant research efforts have been conducted in elucidating the process of revascularization and the influence of engraftment site on graft function and survival. During the isolation process the intrinsic islet vascular networks are destroyed, leading to impaired revascularization after transplant. As a result, in some cases a significant quantity of the beta cell mass transplanted dies acutely following the infusion into the portal vein, the most clinically used site of engraftment. Subsequently, despite the majority of patients achieving insulin independence after transplant, a proportion of them recommence small, supplemental exogenous insulin over time. Herein, this review considers the process of islet revascularization after transplant, its limiting factors, and potential strategies to improve this critical step. Furthermore, we provide a characterization of alternative transplant sites, analyzing the historical evolution and their role towards advancing transplant outcomes in both the experimental and clinical settings.

Transgene and islet cell delivery systems using nano-sized carriers for the treatment of diabetes mellitus

“…With regard to islet cell transplantation sites, intramuscular and subcutaneous spaces are considered to be clinically better because they are highly accessible and less invasive [91,93]. However, hypoxic conditions in intramuscular and subcutaneous spaces have been reported to reduce the survival of transplanted islet cells [94–96].…”

Strategies in Preventing Diabetes after Pancreatectomy Using Islet Auto- and Allo-Transplantation

“…Clinically, the peritoneal cavity is currently undergoing trials mainly for encapsulated islets [67]. There's a delay in systemic insulin distribution from islets placed in the peritoneal cavity [68], and a significantly larger number of islets is needed to result in cure when compared to intraportal transplantation [66].…”

A Novel Pre-Vascularized Subcutaneous Site Safely Accommodates Stem Cell Derived Therapies for Treating Diabetes

“…The focus is now on optimizing the existing differentiation protocols to allow for a successful and stable diabetes reversal. However, finding the most efficient transplant site remains a dilemma given the infusion volume needed at the time of transplant and the potential need for graft retrieval in the event of tumor formation [7,8]. These reasons are a deterrent to use the conventional intra portal route for this transplantation modality.…”