Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15219, USA.
Biomech Model Mechanobiol. 2011 Dec;10(6):939-53. doi: 10.1007/s10237-010-0285-8. Epub 2011 Jan 21.
Mesenchymal stem cell (MSC) therapy has demonstrated applications in vascular regenerative medicine. Although blood vessels exist in a mechanically dynamic environment, there has been no rigorous, systematic analysis of mechanical stimulation on stem cell differentiation. We hypothesize that mechanical stimuli, relevant to the vasculature, can differentiate MSCs toward smooth muscle (SMCs) and endothelial cells (ECs). This was tested using a unique experimental platform to differentially apply various mechanical stimuli in parallel. Three forces, cyclic stretch, cyclic pressure, and laminar shear stress, were applied independently to mimic several vascular physiologic conditions. Experiments were conducted using subconfluent MSCs for 5 days and demonstrated significant effects on morphology and proliferation depending upon the type, magnitude, frequency, and duration of applied stimulation. We have defined thresholds of cyclic stretch that potentiate SMC protein expression, but did not find EC protein expression under any condition tested. However, a second set of experiments performed at confluence and aimed to elicit the temporal gene expression response of a select magnitude of each stimulus revealed that EC gene expression can be increased with cyclic pressure and shear stress in a cell-contact-dependent manner. Further, these MSCs also appear to express genes from multiple lineages simultaneously which may warrant further investigation into post-transcriptional mechanisms for controlling protein expression. To our knowledge, this is the first systematic examination of the effects of mechanical stimulation on MSCs and has implications for the understanding of stem cell biology, as well as potential bioreactor designs for tissue engineering and cell therapy applications.
间充质干细胞（MSC）疗法在血管再生医学中具有应用潜力。尽管血管存在于机械动态环境中，但目前尚未对机械刺激对干细胞分化的影响进行严格、系统的分析。我们假设与脉管系统相关的机械刺激可以将 MSCs 分化为平滑肌（SMCs）和内皮细胞（ECs）。我们使用一种独特的实验平台来同时平行地施加各种机械刺激来检验这一假说。通过独立施加三种力，即循环拉伸、循环压力和层流剪切应力，来模拟多种血管生理条件。实验使用亚汇合的 MSC 进行了 5 天，结果表明，刺激的类型、幅度、频率和持续时间对形态和增殖有显著影响。我们已经确定了循环拉伸的阈值，这些阈值可以增强 SMC 蛋白的表达，但在测试的任何条件下都没有发现 EC 蛋白的表达。然而，在另一组在汇合状态下进行的实验中，旨在引发每种刺激的特定幅度的时程基因表达反应，结果表明，EC 基因表达可以通过循环压力和剪切应力以细胞接触依赖的方式增加。此外，这些 MSC 似乎还同时表达多个谱系的基因，这可能需要进一步研究控制蛋白质表达的转录后机制。据我们所知，这是首次对机械刺激对 MSC 的影响进行系统研究，对理解干细胞生物学以及组织工程和细胞治疗应用的潜在生物反应器设计具有重要意义。
