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干细胞力学生物学的新视角:干细胞行为和命运的生物力学控制

A new perspective for stem-cell mechanobiology: biomechanical control of stem-cell behavior and fate.

作者信息

Titushkin Igor A, Shin Jennifer, Cho Michael

机构信息

Bioengineering Department, University of Illinois, Chicago, USA.

出版信息

Crit Rev Biomed Eng. 2010;38(5):393-433. doi: 10.1615/critrevbiomedeng.v38.i5.10.

DOI:10.1615/critrevbiomedeng.v38.i5.10
PMID:21175407
Abstract

Biomechanics is known to play an important role in cell metabolism. Cell phenotype, tissue-specific functions, and fate critically depend on the extracellular mechanical environment. The mechanical properties of the cell itself, such as cytoskeleton elasticity, membrane tension, and adhesion strength, may also play an important role in cell homeostasis and differentiation. Pluripotent bone marrow-derived human mesenchymal stem cells, for example, can be differentiated into many tissue-specific lineages. While cellular biomechanical properties are significantly altered during stem-cell specification to a particular phenotype, the complexity of events associated with transformation of these precursor cells leaves many questions unanswered about morphological, structural, proteomic, and functional changes in differentiating stem cells. A thorough understanding of stem-cell behavior would allow the development of more effective approaches to the expansion of stem cells in vitro and the regulation of their commitment to a specific phenotype. Control of cell behaviors might be feasible through manipulation of the cellular biomechanical properties using various external physical stimuli, including electric fields, mechanical stimuli, and genetic manipulation of the expression of particular genes. Biomechanical regulation of stem-cell differentiation can greatly minimize the number of chemicals and growth factors that would otherwise be required for composite tissue engineering. Determination and the appropriate use of the known physicochemical cues will facilitate current research effort toward designing and engineering functional tissue constructs.

摘要

众所周知,生物力学在细胞代谢中发挥着重要作用。细胞表型、组织特异性功能和命运严重依赖于细胞外机械环境。细胞自身的力学特性,如细胞骨架弹性、膜张力和黏附强度,在细胞稳态和分化中也可能起重要作用。例如,多能性骨髓来源的人间充质干细胞可以分化为许多组织特异性谱系。虽然在干细胞向特定表型分化过程中细胞生物力学特性会发生显著改变,但与这些前体细胞转化相关的事件的复杂性使得关于分化干细胞的形态、结构、蛋白质组学和功能变化仍有许多问题未得到解答。对干细胞行为的透彻理解将有助于开发更有效的方法来体外扩增干细胞并调节其向特定表型的定向分化。通过使用各种外部物理刺激,包括电场、机械刺激和对特定基因表达的基因操作来操纵细胞生物力学特性,可能实现对细胞行为的控制。干细胞分化的生物力学调节可以极大地减少复合组织工程中原本所需的化学物质和生长因子的数量。确定并适当使用已知的物理化学线索将促进当前设计和构建功能性组织构建体的研究工作。

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