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| Item Type: | Article |
|---|---|
| Title: | Engineered vasculature induces functional maturation of pluripotent stem cell-derived islet organoids |
| Creators: |
Jun, Yesl, Nguyen-Ngoc, Kim-Vy, Sai, Somesh  ORCID: https://orcid.org/0000-0001-6865-341X, Bender, R. Hugh F., Gong, Winnie, Kravets, Vira, Zhu, Han, Hatch, Christopher J., Schlichting, Michael, Gaetani, Roberto, Mallick, Medhavi, Hachey, Stephanie J., Christman, Karen L., George, Steven C., Hughes, Christopher C.W. and Sander, Maike ORCID: https://orcid.org/0000-0001-5308-7785
|
| 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 |
| Volume: | 60 |
| Number: | 18 |
| Page Range: | 2455-2469.e7 |
| Date: | 22 September 2025 |
| Official Publication: | https://doi.org/10.1016/j.devcel.2025.04.024 |
| PubMed: | View item in PubMed |
| Related to: |
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