Methods for Generating Vascularized Islet-Like Organoids Via Self-Condensation

Abstract

Despite the promise of emerging organoid-based approaches, building additional complexity, such as the vascular network, remains a major challenge toward regenerative therapy. Recently, we developed a complex organoid engineering method by "self-condensation," wherein mesenchymal cell–dependent contraction enables large-scale condensation from heterotypic multiple progenitors. Here, we describe the adaptation of this protocol for generating three-dimensional (3D) pancreatic condensates from dissociated β cell lines (MIN6) together with blood vessel–forming progenitors. This protocol achieves 3D pancreatic islet-like organoid self-organization with endothelialized networks through mesenchymal stem cell–dependent contraction. Transplantation of pancreatic islet-like organoids treats diabetes in mice effectively. Given the donor shortage associated with clinical islet transplantation, our approach offers a promising alternative toward therapeutic organoid transplantation. © 2018 by John Wiley & Sons, Inc.