Journal
CELL STEM CELL
Volume 26, Issue 2, Pages 251-+Publisher
CELL PRESS
DOI: 10.1016/j.stem.2019.12.012
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Funding
- NIH (United States) [F31-HL143924, T32-GM0007324, 1R01HL116705]
- CRMRF (United States) [12-SCB-YALE-06, 15-RMB-YALE-08]
- AHA (United States) [19POST34450100]
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Vascular smooth muscle cells (VSMCs) can be derived in large numbers from human induced pluripotent stem cells (hiPSCs) for producing tissue-engineered vascular grafts (TEVGs). However, hiPSC-derived TEVGs are hampered by low mechanical strength and significant radial dilation after implantation. Here, we report generation of hiPSC-derived TEVGs with mechanical strength comparable to native vessels used in arterial bypass grafts by utilizing biodegradable scaffolds, incremental pulsatile stretching, and optimal culture conditions. Following implantation into a rat aortic model, hiPSC-derived TEVGs show excellent patency without luminal dilation and effectively maintain mechanical and contractile function. This study provides a foundation for future production of non-immunogenic, cellularized hiPSC-derived TEVGs composed of allogenic vascular cells, potentially serving needs to a considerable number of patients whose dysfunctional vascular cells preclude TEVG generation via other methods.
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