Tissue-Engineered Vascular Grafts with Advanced Mechanical Strength from Human iPSCs
Tissue-Engineered Vascular Grafts with Advanced Mechanical Strength from Human iPSCs
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DOI：
10.1016/j.stem.2019.12.012
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发表时间：
2020-02-06
期刊：
影响因子：
23.9
通讯作者：
Qyang, Yibing
中科院分区：
文献类型：
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作者：
Luo, Jiesi;Qin, Lingfeng;Qyang, Yibing
血管平滑肌细胞（VSMC）可以大量来源于人诱导多能干细胞（hiPSC），用于产生组织工程化血管移植物（TEVG）。然而，hiPSC衍生的TEVG受到植入后低机械强度和显著径向扩张的阻碍。在这里，我们报告了hiPSC衍生的TEVG的产生，其机械强度与动脉旁路移植术中使用的天然血管相当，通过利用可生物降解的支架，增量脉动拉伸和最佳培养条件。在植入大鼠主动脉模型后，hiPSC衍生的TEVG显示出优异的通畅性而没有管腔扩张，并有效地维持机械和收缩功能。本研究为将来生产由同种异体血管细胞组成的非免疫原性、细胞化hiPSC衍生的TEVG提供了基础，可能满足相当多的患者的需求，这些患者的功能障碍性血管细胞阻止了通过其他方法产生TEVG。
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.