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 Cellular and Molecular Physiology, Yale University, New Haven, CT 06519, USA.
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.
J Mol Cell Cardiol. 2022 Feb;163:167-174. doi: 10.1016/j.yjmcc.2021.12.014. Epub 2021 Dec 31.
Tissue engineered vascular grafts possess several advantages over synthetic or autologous grafts, including increased availability and reduced rates of infection and thrombosis. Engineered grafts constructed from human induced pluripotent stem cell derivatives further offer enhanced reproducibility in graft production. One notable obstacle to clinical application of these grafts is the lack of elastin in the vessel wall, which would serve to endow compliance in addition to mechanical strength. This study establishes the ability of the polyphenol compound epigallocatechin gallate, a principal component of green tea, to facilitate the extracellular formation of elastin fibers in vascular smooth muscle cells derived from human induced pluripotent stem cells. Further, this study describes the creation of a doxycycline-inducible elastin expression system to uncouple elastin production from vascular smooth muscle cell proliferative capacity to permit fiber formation in conditions conducive to robust tissue engineering.
组织工程血管移植物相对于合成或自体移植物具有多种优势,包括可用性增加,感染和血栓形成的风险降低。由人诱导多能干细胞衍生物构建的工程移植物进一步提高了移植物生产的重现性。这些移植物临床应用的一个显著障碍是血管壁缺乏弹性蛋白,这除了提供机械强度外,还将赋予顺应性。本研究确立了多酚化合物表没食子儿茶素没食子酸酯(绿茶的主要成分)促进人诱导多能干细胞来源的血管平滑肌细胞中外源性弹性蛋白纤维形成的能力。此外,本研究描述了创建一种强力霉素诱导的弹性蛋白表达系统,以将弹性蛋白的产生与血管平滑肌细胞增殖能力解耦,从而在有利于组织工程的条件下促进纤维形成。