Engineered vasculature induces functional maturation of pluripotent stem cell-derived islet organoids

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Item Type:	Preprint
Title:	Engineered vasculature induces functional maturation of pluripotent stem cell-derived islet organoids
Creators Name:	Nguyen-Ngoc, K.V., Jun, Y., Sai, S., Bender, R.H.F., Kravets, V., Zhu, H., Hatch, C.J., Schlichting, M., Gaetani, R., Mallick, M., Hachey, S.J., Christman, K.L., George, S.C., Hughes, C.C.W. and Sander, M.
Abstract:	Blood vessels play a critical role in pancreatic islet health and function, yet current culture methods to generate islet organoids from human pluripotent stem cells (SC-islets) lack a vascular component. Here, we engineered 3D vascularized SC-islet organoids by assembling SC-islet cells, human primary endothelial cells (ECs) and fibroblasts both in a non-perfused model and a microfluidic device with perfused vessels. Vasculature improved stimulus-dependent Ca2+ influx into SC-β-cells, a hallmark of β-cell function that is blunted in non-vascularized SC-islets. We show that an islet-like basement membrane is formed by vasculature and contributes to the functional improvement of SC-β-cells. Furthermore, cell-cell communication networks based on scRNA-seq data predicted BMP2/4-BMPR2 signaling from ECs to SC-β-cells. Correspondingly, BMP4 augmented the SC-β-cell Ca2+ response and insulin secretion. These vascularized SC-islet models will enable further studies of crosstalk between β-cells and ECs and can serve as in vivo-mimicking platforms for disease modeling and therapeutic testing.
Keywords:	Organoid, Islet, Human Embryonic Stem Cells, Vasculature, Endothelial Cells, Β-cells, Microfluidic Device, Ca2+ Imaging
Source:	bioRxiv
Publisher:	Cold Spring Harbor Laboratory Press
Article Number:	2022.10.28.513298
Date:	30 October 2022
Official Publication:	https://doi.org/10.1101/2022.10.28.513298

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