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

EMBO molecular medicine 2021 Jan 11

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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. © 2020 The Authors. Published under the terms of the CC BY 4.0 license.

Citation

Lisa Nalbach, Leticia P Roma, Beate M Schmitt, Vivien Becker, Christina Körbel, Selina Wrublewsky, Mandy Pack, Thomas Später, Wolfgang Metzger, Maximilian M Menger, Florian S Frueh, Claudia Götz, Haopeng Lin, Joseline E Manning Fox, Patrick E MacDonald, Michael D Menger, Matthias W Laschke, Emmanuel Ampofo. Improvement of islet transplantation by the fusion of islet cells with functional blood vessels. EMBO molecular medicine. 2021 Jan 11;13(1):e12616