Wang James H-C, Thampatty Bhavani P
Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.
Int Rev Cell Mol Biol. 2008;271:301-46. doi: 10.1016/S1937-6448(08)01207-0.
Mechanical forces, including gravity, tension, compression, hydrostatic pressure, and fluid shear stress, play a vital role in human physiology and pathology. They particularly influence extracellular matrix (ECM) gene expression, ECM protein synthesis, and production of inflammatory mediators of many load-sensitive adult cells such as fibroblasts, chondrocytes, smooth muscle cells, and endothelial cells. Furthermore, the mechanical forces generated by cells themselves, known as cell traction forces (CTFs), also influence many biological processes such as wound healing, angiogenesis, and metastasis. Thus, the quantitative characterization of CTFs by qualities such as magnitude and distribution is useful for understanding physiological and pathological events at the tissue and organ levels. Recently, the effects of mechanical loads on embryonic and adult stem cells in terms of self-renewal, differentiation, and matrix protein expression have been investigated. While it seems certain that mechanical loads applied to stem cells regulate their self-renewal and induce controlled cell lineage differentiation, the detailed molecular signaling mechanisms responsible for these mechano-effects remain to be elucidated. Challenges in the fields of both adult- and stem-cell mechanobiology include devising novel experimental and theoretical methodologies to examine mechano-responses more closely to various forms of mechanical forces and mechanotransduction mechanisms of these cells in a more physiologically accurate setting. Such novel methodologies will lead to better understanding of various pathological diseases, their management, and translational applications in the ever expanding field of tissue engineering.
机械力,包括重力、张力、压力、流体静压和流体剪切应力,在人体生理和病理过程中起着至关重要的作用。它们尤其会影响细胞外基质(ECM)基因表达、ECM蛋白质合成以及许多对负荷敏感的成年细胞(如成纤维细胞、软骨细胞、平滑肌细胞和内皮细胞)炎症介质的产生。此外,细胞自身产生的机械力,即细胞牵引力(CTF),也会影响许多生物学过程,如伤口愈合、血管生成和转移。因此,通过大小和分布等特性对CTF进行定量表征,有助于理解组织和器官水平上的生理和病理事件。最近,人们研究了机械负荷对胚胎干细胞和成年干细胞在自我更新、分化和基质蛋白表达方面的影响。虽然施加于干细胞的机械负荷似乎确实能调节其自我更新并诱导可控的细胞谱系分化,但导致这些机械效应的详细分子信号机制仍有待阐明。成体干细胞和干细胞力学生物学领域的挑战包括设计新的实验和理论方法,以便在更符合生理实际的环境中更密切地研究对各种形式机械力的机械反应以及这些细胞的机械转导机制。此类新方法将有助于更好地理解各种病理疾病、其治疗方法以及在不断扩展的组织工程领域中的转化应用。