细胞外基质硬度调控间充质干细胞分化

Extracellular Matrix Stiffness Modulates the Differentiation of Mesenchymal Stem Cells

新近研究表明,细胞外基质(extracellular matrix,ECM)的物理性质,特别是硬度或弹性,能对细胞的黏附、铺展、迁移、增殖、分化和凋亡等多种功能和行为产生重要影响。间充质干细胞(mesenchymal stem cells,MSCs)是组织工程和细胞治疗的理想种子细胞。ECM硬度可诱导MSCs向脂肪、软骨、神经、肌肉和骨等方向分化。该文综合论述了ECM硬度对干细胞分化的影响,涵盖了构建ECM硬度的测量、调控与表征等,不同培养条件下干细胞对硬度的响应和分化以及硬度和其他因素的联合作用;在此基础上,进一步论述了干细胞分化过程中细胞感应ECM硬度并转化为生物学信号的机制和信号通路。该文还总结了在ECM硬度调控干细胞分化行为领域最新的研究进展情况,较为系统地分析了材料学、细胞生物学、分子生物学水平的主要影响因素,并对本领域未来需要重点研究的问题进行了展望。

Recent studies have suggested that the physical characteristics of extracellular matrix （ECM）, especially the stiffness or elasticity, played an important role in regulating cellular functions and behaviors, including adhesion, spreading, migration, proliferation, differentiation, apoptosis and so on. Mesenchymal stem cells （MSCs） are important for cell therapy and tissue engineering. ECM stiffness can induce MSCs into cells of adipose tissue, cartilage, nerve, muscle, bone and others. This review discussed the studies of the effect of ECM stiffness on stem cell lineage specification, covering the materials and techniques to fabricate substrates, methods of controlling stiffness, properties, the response to ECM stiffness and the differentiation of stem cells in different culture conditions, as well as the combined effect of ECM stiffness and other biophysical and biochemical cues; On this basis, we further shed light on the mechanism and the signaling pathway of the reaction of stem cells to ECM stiffness and transduction of stiffness to biological signals during differentiation. This review summarized the latest research advancement in the field of differentiation behavior of stem cells modulated by ECM stiffnessand presented a relatively systematic analysis of the major factors in the level of materials science, cell biology and molecular biology, as well as the prospects of some key problems to be studied in this field.