Monitoring mesenchymal stromal cell developmental stage to apply on-time mechanical stimulation for ligament tissue engineering
Monitoring mesenchymal stromal cell developmental stage to apply on-time mechanical stimulation for ligament tissue engineering
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DOI：
10.1089/ten.2006.12.3085
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发表时间：
2006-11-01
影响因子：
--
通讯作者：
Altman, Gregory H.
中科院分区：
文献类型：
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作者：
Chen, Jingsong;Horan, Rebecca L.;Altman, Gregory H.
为了评估在韧带组织工程中施加机械刺激以诱导间充质干细胞（MSC）分化的合适时间框架，在体外培养期间对发育细胞表型进行了监测。将间充质干细胞接种到表面改性的丝素纤维基质上，并在培养皿中培养15天。在间充质干细胞培养过程中，对细胞代谢活性、形态以及细胞外基质（ECM）蛋白（Ⅰ型和Ⅲ型胶原蛋白以及纤连蛋白）、ECM受体（整合素α - 2、α - 5和β - 1）和热休克蛋白70（HSP - 70）的基因表达进行了监测。间充质干细胞在细胞代谢活性、细胞外基质、整合素和HSP - 70转录方面表现出波动，这可能与内在的发育过程相关。细胞对机械刺激的反应取决于细胞发育阶段。在第9天，当细胞代谢活性、细胞外基质、整合素和HSP - 70转录水平达到峰值时，机械刺激增加了间充质干细胞的代谢活性、排列以及胶原蛋白的产生。在第1天和第3天施加机械刺激对接种在丝基质上的间充质干细胞显示出有害影响。本研究中呈现的结果确定了在表面改性的丝基质上间充质干细胞的内在发育过程与动态环境信号之间的独特相关性。
To evaluate the appropriate time frame for applying mechanical stimuli to induce mesenchymal stromal cell ( MSC) differentiation for ligament tissue engineering, developmental cell phenotypes were monitored during a period of in vitro culture. MSCs were seeded onto surface-modified silk fibroin fiber matrices and cultured in Petri dishes for 15 days. Cell metabolic activity, morphology, and gene expression of extracellular matrix (ECM) proteins ( collagen type I and III and fibronectin), ECM receptors (integrins alpha-2, alpha-5, and beta-1), and heat- shock protein 70 ( HSP-70) were monitored during the culture of MSC. MSCs showed fluctuations in cell metabolic activity, ECM, integrin, and HSP-70 transcription potentially correlating to innate developmental processes. Cellular response to mechanical stimulation was dependent on the stage of cell development. At day 9, when levels of cell metabolic activity, ECM, integrin, and HSP-70 transcription peaked, mechanical stimulation increased MSC metabolic activity, alignment, and collagen production. Mechanical stimulation applied at day 1 and 3 showed detrimental effects on MSCs seeded on silk matrices. The results presented in this study identify a unique correlation between innate MSC development processes on a surface-modified silk matrix and dynamic environmental signaling.