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基于人诱导多能干细胞的具有先进机械强度的组织工程血管移植物。

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

机构信息

Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, CT 06511, USA; Yale Stem Cell Center, New Haven, CT 06520, USA.

Department of Surgery, Yale University, New Haven, CT 06520, USA.

出版信息

Cell Stem Cell. 2020 Feb 6;26(2):251-261.e8. doi: 10.1016/j.stem.2019.12.012. Epub 2020 Jan 16.

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.

摘要

血管平滑肌细胞(VSMCs)可以从人诱导多能干细胞(hiPSCs)中大量获得,用于制造组织工程血管移植物(TEVGs)。然而,hiPSC 衍生的 TEVGs 存在机械强度低和植入后显著径向扩张的问题。在这里,我们通过利用可生物降解的支架、递增式脉动拉伸和优化的培养条件,报告了具有与用于动脉旁路移植术的天然血管相当的机械强度的 hiPSC 衍生 TEVGs 的产生。在植入大鼠主动脉模型后,hiPSC 衍生的 TEVGs 显示出优异的通畅性,没有管腔扩张,并有效地维持机械和收缩功能。这项研究为未来生产由同种异体血管细胞组成的、无免疫原性、细胞化的 hiPSC 衍生 TEVGs 提供了基础,可能满足大量患者的需求,这些患者的功能失调的血管细胞通过其他方法无法生成 TEVG。

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