Self-Condensation Culture Enables Vascularization of Tissue Fragments for Efficient Therapeutic Transplantation
Date: 9 May 2018
Self-condensation culture enables endothelialization of diverse tissue fragments
Vascularization facilitates tissue survival after transplantation
Vascularized islet transplant enhances therapeutic potential against diabetes
Rapid induction of functional vasculatures preserves original islet architecture
Clinical transplantation of tissue fragments, including islets, faces a critical challenge because of a lack of effective strategies that ensure efficient engraftment through the timely integration of vascular networks. We recently developed a complex organoid engineering method by “self-condensation” culture based on mesenchymal cell-dependent contraction, thereby enabling dissociated heterotypic lineages including endothelial cells to self-organize in a spatiotemporal manner. Here, we report the successful adaptation of this method for generating complex tissues from diverse tissue fragments derived from various organs, including pancreatic islets. The self-condensation of human and mouse islets with endothelial cells not only promoted functionalization in culture but also massively improved post-transplant engraftment. Therapeutically, fulminant diabetic mice were more efficiently treated by a vascularized islet transplant compared with the conventional approach. Given the general limitations of post-transplant vascularization associated with 3D tissue-based therapy, our approach offers a promising means of enhancing efficacy in the context of therapeutic tissue transplantation.
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