Tissue-Engineered Vascular Grafts with Advanced Mechanical Strength from Human iPSCs

人类 iPSC 制成的具有高机械强度的组织工程血管移植物

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作者:Jiesi Luo, Lingfeng Qin, Liping Zhao, Liqiong Gui, Matthew W Ellis, Yan Huang, Mehmet H Kural, J Alexander Clark, Shun Ono, Juan Wang, Yifan Yuan, Shang-Min Zhang, Xiaoqiang Cong, Guangxin Li, Muhammad Riaz, Colleen Lopez, Akitsu Hotta, Stuart Campbell, George Tellides, Alan Dardik, Laura E Niklason

Abstract

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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