AUTHOR=Wassmer Charles-Henri , Lebreton Fanny , Bellofatto Kevin , Perez Lisa , Cottet-Dumoulin David , Andres Axel , Bosco Domenico , Berney Thierry , Othenin-Girard Véronique , Martinez De Tejada Begoña , Cohen Marie , Olgasi Christina , Follenzi Antonia , Berishvili Ekaterine ,  the VANGUARD Consortium , Borsotti Chiara , Merlin Simone , Piemonti Lorenzo , Citro Antonio , Pellegrini Silvia , Seissler Jochen , Wolf-van Buerck Lelia , Honarpisheh Mohsen , Thaunat Olivier , Massey Emma , Cronin Antonia , Bunnik Eline , de Jongh Dide , Segantini Luca , Rossi Giovanna , Kugelmeier Patrick , Wolint Petra , Cavallaro Marco , Götz Julia , Müller Jeanette 

TITLE=Bio-Engineering of Pre-Vascularized Islet Organoids for the Treatment of Type 1 Diabetes

JOURNAL=Transplant International

VOLUME=Volume 35 - 2021

YEAR=2022

URL=https://www.frontierspartnerships.org/journals/transplant-international/articles/10.3389/ti.2021.10214

DOI=10.3389/ti.2021.10214

ISSN=1432-2277

ABSTRACT=Lack of rapid revascularization and inflammatory attacks at the site of transplantation contribute to impaired islet engraftment and suboptimal metabolic control after clinical islet transplantation. In order to overcome these limitations and enhance engraftment and revascularization, we have generated and transplanted pre-vascularized insulin-secreting organoids composed of rat islet cells, human amniotic epithelial cells (hAECs), and human umbilical vein endothelial cells (HUVECs). Our study demonstrates that pre-vascularized islet organoids exhibit enhanced in vitro function compared to native islets, and, most importantly, better engraftment and improved vascularization in vivo in a murine model. This is mainly due to cross-talk between hAECs, HUVECs and islet cells, mediated by the upregulation of genes promoting angiogenesis (vegf-a) and beta cell function (glp-1r, pdx1). The possibility of adding a selected source of endothelial cells for the neo-vascularization of insulin-scereting grafts may also allow implementation of beta cell replacement therapies in more favourable transplantation sites than the liver.