The guidance of stem cell differentiation by substrate alignment and mechanical stimulation.
The guidance of stem cell differentiation by substrate alignment and mechanical stimulation.
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通过底物比对和机械刺激对干细胞分化的引导。
DOI：
10.1016/j.biomaterials.2012.11.012
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发表时间：
2013-03
期刊：
影响因子：
14
通讯作者：
Lu, Helen H.
中科院分区：
文献类型：
--
作者：
Subramony, Siddarth D.;Dargis, Booth R.;Castillo, Mario;Azeloglu, Evren U.;Tracey, Michael S.;Su, Amanda;Lu, Helen H.
间充质干细胞(MSC)是一种具有良好临床应用前景的组织工程细胞来源。因此，由于机械、化学和结构信号在复杂分化过程中的作用在很大程度上尚不清楚，因此引导MSCs向维持这些表型的特定谱系方向尤其具有挑战性。为了充分利用MSCs用于再生医学的潜力，需要对这些刺激的单独和联合影响进行系统研究。此外，与难以控制时间和浓度梯度的化学刺激不同，机械刺激和基于支架的线索可能相对更具仿生性，可以更好地控制以确保MSC分化的保真度。本研究的目的是研究纳米纤维基质排列和机械刺激在MSC分化中的作用，重点阐明每个参数在引导功能性结缔组织再生中的相对贡献。据观察，纳米纤维的排列引导MSC对生理负荷的反应，成纤维细胞的分化需要与生理相关的细胞-材料相互作用和机械刺激的组合。重要的是，这项研究的结果表明，系统性和容易控制的信号，如支架排列和优化的机械刺激，足以推动MSC分化，而不需要额外的化学刺激。此外，这些发现还产生了一套基本的设计规则，可以很容易地应用于结缔组织再生策略。
Mesenchymal stem cells (MSC) represent a promising and clinically relevant cell source for tissue engineering applications. As such, guiding MSCs towards specific lineages maintaining these phenotypes has been particularly challenging as the contributions of mechanical, chemical and structural cues to the complex differentiation process are largely unknown. To fully harness the potential of MSCs for regenerative medicine, a systematic investigation into the individual and combined effects of these stimuli is needed. In addition, unlike chemical stimulation, for which temporal and concentration gradients are difficult to control, mechanical stimulation and scaffold-based cues may be relatively more biomimetic and can be applied with greater control to ensure fidelity in MSC differentiation. The objective of this study is to investigate the role of nanofiber matrix alignment and mechanical stimulation on MSC differentiation, focusing on elucidating the relative contribution of each parameter in guided regeneration of functional connective tissues. It is observed nanofiber alignment directs MSC response to physiological loading and that fibroblastic differentiation requires a combination of physiologically-relevant cell-material interactions in conjunction with mechanical stimulation. Importantly, the results of this study reveal that systemic and readily controllable cues, such as scaffold alignment and optimized mechanical stimulation, are sufficient to drive MSC differentiation, without the need for additional chemical stimuli. Moreover, these findings also yield a set of fundamental design rules can be readily applied to connective tissue regeneration strategies.
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