Improvement of islet transplantation by the fusion of islet cells with functional blood vessels

Pancreatic islet transplantation still represents a promising therapeutic strategy for curative treatment of type 1 diabetes mellitus. However, a limited number of organ donors and insufficient vascularization with islet engraftment failure restrict the successful transfer of this approach into clinical practice. To overcome these problems, we herein introduce a novel strategy for the generation of prevascularized islet organoids by the fusion of pancreatic islet cells with functional native microvessels. These insulin‐secreting organoids exhibit a significantly higher angiogenic activity compared to freshly isolated islets, cultured islets, and non‐prevascularized islet organoids. This is caused by paracrine signaling between the β‐cells and the microvessels, mediated by insulin binding to its corresponding receptor on endothelial cells. In vivo , the prevascularized islet organoids are rapidly blood‐perfused after transplantation by the interconnection of their autochthonous microvasculature with surrounding blood vessels. As a consequence, a lower number of islet grafts are required to restore normoglycemia in diabetic mice. Thus, prevascularized islet organoids may be used to improve the success rates of clinical islet transplantation. Synopsis This study introduces a novel strategy to accelerate the revascularization of transplanted islets by the fusion of microvascular fragments (MVF) with pancreatic islet cells. These prevascularized islet organoids may be used to improve the success rate of clinical islet transplantation. The fusion of islet cells with MVF resulted in compact prevascularized islet organoids. Prevascularized islet organoids exhibited a highly angiogenic activity, mediated by a paracrine signaling between β‐cells and endothelial cells. The transplantation of prevascularized islet organoids restored normoglycemia in diabetic animals immediately after transplantation. Graphical Abstract This study introduces a novel strategy to accelerate the revascularization of transplanted islets by the fusion of microvascular fragments (MVF) with pancreatic islet cells. These prevascularized islet organoids may be used to improve the success rate of clinical islet transplantation.