Trinity Centre for Biomedical Engineering, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland; Department of Mechanical & Manufacturing Engineering, School of Engineering, Trinity College Dublin, Dublin, Ireland.
School of Biotechnology, Vascular Biology & Therapeutics Group, Dublin City University, Glasnevin, Dublin 9, Ireland.
Biochem Biophys Res Commun. 2020 Jan 15;521(3):762-768. doi: 10.1016/j.bbrc.2019.10.185. Epub 2019 Nov 6.
Atherosclerosis is one of the leading causes of mortality worldwide, and presents as a narrowing or occlusion of the arterial lumen. Interventions to re-open the arterial lumen can result in re-occlusion through intimal hyperplasia. Historically only de-differentiated vascular smooth muscle cells were thought to contribute to intimal hyperplasia. However recent significant evidence suggests that resident medial multipotent vascular stem cells (MVSC) may also play a role. We therefore investigated the strain response of MVSC since these resident cells are also subjected to strain within their native environment. Accordingly, we applied uniaxial 1 Hz cyclic uniaxial tensile strain at three amplitudes around a mean strain of 5%, (4-6%, 2-8% and 0-10%) to either rat MVSC or rat VSMC before their strain response was evaluated. While both cell types strain avoid, the strain avoidant response was greater for MVSC after 24 h, while VSMC strain avoid to a greater degree after 72 h. Additionally, both cell types increase strain avoidance as strain amplitude is increased. Moreover, MVSC and VSMC both demonstrate a strain-induced decrease in cell number, an effect more pronounced for MVSC. These experiments demonstrate for the first time the mechano-sensitivity of MVSC that may influence intimal thickening, and emphasizes the importance of strain amplitude in controlling the response of vascular cells in tissue engineering applications.
动脉粥样硬化是全球主要的死亡原因之一，表现为动脉管腔狭窄或闭塞。为重新开放动脉管腔而进行的干预可能会导致内膜增生导致再闭塞。历史上，只有去分化的血管平滑肌细胞被认为有助于内膜增生。然而，最近有重要证据表明，常驻中膜多能血管干细胞（MVSC）也可能起作用。因此，我们研究了 MVSC 的应变响应，因为这些常驻细胞在其天然环境中也会受到应变的影响。相应地，我们在三种平均应变（5%左右）下应用 1Hz 的单轴循环单轴拉伸应变，分别为 4-6%、2-8%和 0-10%，然后评估它们的应变响应。虽然两种细胞类型都避免应变，但 MVSC 在 24 小时后的应变回避反应更大，而 VSMC 在 72 小时后的应变回避反应更大。此外，随着应变幅度的增加，两种细胞类型都增加了应变回避。此外，MVSC 和 VSMC 都表现出细胞数量因应变而减少的现象，对于 MVSC 来说，这种效应更为明显。这些实验首次证明了 MVSC 的力学敏感性，这可能会影响内膜增厚，并强调了在组织工程应用中控制血管细胞反应时应变幅度的重要性。
