Abstract:

Mesenchymal stem cells (MSCs) are capable of self-replication and multi-directional differentiation, which are very important for the development and reconstruction of mesenchymal tissue. Bone tissue damage repair involves the participation of various cells and molecules. The recovery of bone mass requires sufficiently many MSCs to migrate to the damaged site to perform the reconstruction function. The local inflammatory response at the injury site can recruit MSCs and promote new bone formation. Simultaneously, niche changes during the migration of MSCs will affect their biological performance and initiate the phase of directed differentiation. This article explores the relevant mechanisms that mediate the migration of MSCs in the process of bone injury repair, including the regulation of immune cells and chemotactic signaling molecules in the inflammatory response in the bone repair stage through signaling pathways such as BMP/Smads. Then, it summarizes the mechanism by which the high matrix stiffness upregulates the expression of the integrin and focal adhesions to promote the MSCs migration and osteogenic differentiation. Simultaneously, the migration ability of MSCs can be regulated through drugs or genetic modification to promote the bone injury repair. The improvement of MSCs migration ability can shorten the time of bone tissue damage repair and improve the bone quality. This article reviews the role of the MSCs migration ability in bone tissue injury repair to provide a reference for the application of MSCs with high migration ability in the fields of stem cell therapy for bone related diseases and bone tissue engineering.

Key words: bone injury, bone tissue engineering, stem cell therapy, osteoporosis, osteoarthritis, mesenchymal stem cells, migration, recruitment, homing, integrin, osteogenic differentiation, matrix stiffness

摘要：

间充质干细胞(mesenchymal stem cells,MSCs)具有自我复制和多向分化能力,对间充质组织的发育和重建十分重要。骨组织损伤修复涉及各种细胞、分子的参与,骨量的恢复需要足够MSCs迁移到损伤部位发挥重建功能。目前已经发现损伤部位的局部炎症反应能募集MSCs,促进新骨形成。同时,MSCs迁移过程中生态位的改变也会影响其生物学性能,启动定向分化阶段。本文探讨了骨组织损伤修复过程中介导MSCs迁移的相关机制,包括炎症反应中的免疫细胞和趋化信号分子通过BMP/Smads等信号通路对骨修复阶段的调控作用,并总结了高基质硬度上调整合素以及黏着斑的表达促进MSCs迁移及成骨分化能力的机制。通过药物或者转基因的方式可调控MSCs迁移能力促进骨组织损伤修复,MSCs迁移能力的提高能缩短骨组织损伤修复的时间,提高新生骨质的质量。本文就细胞迁移能力在骨组织损伤修复中的作用进行综述,以期为高迁移能力的MSCs应用于骨相关疾病的干细胞疗法以及骨组织工程领域提供参考。

关键词: 骨组织损伤, 骨组织工程, 干细胞疗法, 骨质疏松症, 骨关节炎, 间充质干细胞, 迁移, 募集, 归巢, 整合素, 成骨分化, 基质硬度