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