Therapeutic Angiogenesis for Islet Revascularization

Successful islet transplantation depends on the infusion of sufficiently large quantities of islets, requiring multiple pancreas donors per recipient. Unfortunately, more than 70% of functional islet mass are lost in the early posttransplantation phase. Unlike whole-organ transplantation by which grafts are implanted as vascularized tissue, islets are transplanted as single islets or islet clusters that are considered avascular. As a result, microvascular perfusion to newly transplanted islets does not resume immediately after transplantation and can take up to weeks until the reestablishment of a functional microvasculature within islet grafts. Delayed and insufficient islet revascularization can deprive newly transplanted islets of oxygen and nutrients, resulting in islet cell death and contributing to early graft failure. There is mounting evidence that impaired islet revascularization constitutes an independent factor that reduces the viability and compromises the function of transplanted islets, thereby limiting the success rate of islet transplantation. In this article, we will review the most recent advances made in deciphering the underlying mechanism of islet revascularization and exploring therapeutic strategies for enhancing islet revascularization and preserving functional islet mass in diabetic recipients.