Human assembloid of human blood vessel organoids with pancreatic islets improves insulin secretion over time ex vivo
Emily Tubbs, Mahira Mehanović, Mélanie Lopes, Clément Quintard, Stéphanie Combe, Clara Pirlian, Mathieu Armanet, Thomas Domet, Julia Sabatier, Sabrina Granziera, Karim Bouzakri, W. Bietiger, Delphine Freida, Josef Penninger, Xavier Gidrol
Abstract
Pancreatic islet transplantation is a promising treatment strategy for type 1 diabetes patients; however, there are still major challenges to overcome, including vascularization. Despite a substantial need to understand the islet graft decline observed in patients 5-10 years post transplantation, clinical translation remains challenging, probably because of species-specific features and the lack of in vitro vascularized models. Here, we report results of a human assembloid composed of self-organizing 3D blood vessel organoids (BVOs) with human pancreatic islets. We demonstrate that co-culture of islets and BVOs ex vivo leads to an auto-organized assembloid (by light-sheet fluorescence microscopy) and improves insulin secretion over time (functionality assays) on 5 independent human islet donors (from 3 different hospital facilities). Taken together, this study could accelerate our understanding of type 1 diabetes and facilitate therapeutic development for type 1 diabetes patients.