Small-diameter artery grafts engineered from pluripotent stem cells maintain 100% patency in an allogeneic rhesus macaque model
Summary
Autologous vascular grafts, the only clinically approved option for small-diameter (<6 mm) revascularizations, require invasive harvesting and have limited availability and variable quality. To address these challenges, we develop a 3-mm-diameter artery graft by using arterial endothelial cells (AECs) derived from pluripotent stem cells (PSCs). After establishing technologies for pure AEC generation and expanded polytetrafluoroethylene (ePTFE) graft coating, we engineer artery grafts by seeding the inner lumen of ePTFE vascular grafts with either major histocompatibility complex (MHC) mismatched unmodified-wild-type (MHC-WT) AECs or MHC class I/II double knockout (MHC-DKO) AECs. Their function is evaluated in a rhesus arterial interposition grafting model. MHC-WT grafts maintained 100% patency for 6 months, significantly better than naked and MHC-DKO grafts. Additionally, the endothelium of MHC-WT grafts is repopulated with host cells, supporting long-term patency. Collectively, our study demonstrates that PSC-derived MHC-WT artery grafts provide an unlimited homogenous resource for allogeneic arterial revascularization. Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.
| Authors | Zhang J, Tabima DM, Vereide D, Zeng W, Albano NJ, Lyon S, Nicksic PJ, Shaffrey EC, George RE, Probasco MD, Perrin ES, Xu Y, Brown ME, Stewart R, Chesler NC, Turng LS, Poore SO, Slukvin II, Thomson JA, Maufort JP |
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| Journal | Cell reports. Medicine |
| Publication Date | 2025 Mar 18;6(3):102002 |
| PubMed | 40068684 |
| PubMed Central | PMC11970380 |
| DOI | 10.1016/j.xcrm.2025.102002 |