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| Item Type: | Article |
|---|---|
| Title: | Engineered vasculature induces functional maturation of pluripotent stem cell-derived islet organoids |
| Creators Name: | Jun, Y., Nguyen-Ngoc, K.V., Sai, S., Bender, R.H.F., Gong, W., 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 function, yet current methods for deriving islet organoids from human pluripotent stem cells (SC-islets) lack vasculature. We engineered three-dimensional (3D) vascularized SC-islet organoids by assembling SC-islet cells, human primary endothelial cells (ECs), and fibroblasts in a non-perfused model and a microfluidic device with perfused vessels. Vasculature improved stimulus-dependent Ca(2+) influx into SC-β cells, a hallmark of β cell function that is blunted in non-vascularized SC-islets. Moreover, vascularization accelerated diabetes reversal post engraftment of a subtherapeutic SC-islet dose into mice. We show that vasculature leads to the formation of an islet-like basement membrane that contributes to the functional improvement of SC-β cells. Furthermore, single-cell RNA sequencing (scRNA-seq) data predicted BMP2/4-BMPR2 signaling from ECs to SC-β cells, and correspondingly, BMP4 enhanced the SC-β cell Ca(2+) response and insulin secretion. Vascularized SC-islets will enable further studies of crosstalk between β cells and ECs and will serve as an in vitro platform for disease modeling and therapeutic testing. |
| Keywords: | Organoid, Islet, Human Pluripotent Stem Cells, Vasculature, Endothelial Cells, Β Cells, Microfluidic Device, Ca(2+) Imaging, Engraftment, Diabetes, Animals, Mice |
| Source: | Developmental Cell |
| ISSN: | 1534-5807 |
| Publisher: | Cell Press / Elsevier |
| Date: | 23 May 2025 |
| Official Publication: | https://doi.org/10.1016/j.devcel.2025.04.024 |
| PubMed: | View item in PubMed |
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