McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Washington University, St Louis, MO, USA.
Translational Musculoskeletal Research Center, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA.
Nat Rev Rheumatol. 2019 Mar;15(3):167-179. doi: 10.1038/s41584-018-0151-0.
Connective tissues within the synovial joints are characterized by their dense extracellular matrix and sparse cellularity. With injury or disease, however, tissues commonly experience an influx of cells owing to proliferation and migration of endogenous mesenchymal cell populations, as well as invasion of the tissue by other cell types, including immune cells. Although this process is critical for successful wound healing, aberrant immune-mediated cell infiltration can lead to pathological inflammation of the joint. Importantly, cells of mesenchymal or haematopoietic origin use distinct modes of migration and thus might respond differently to similar biological cues and microenvironments. Furthermore, cell migration in the physiological microenvironment of musculoskeletal tissues differs considerably from migration in vitro. This Review addresses the complexities of cell migration in fibrous connective tissues from three separate but interdependent perspectives: physiology (including the cellular and extracellular factors affecting 3D cell migration), pathophysiology (cell migration in the context of synovial joint autoimmune disease and injury) and tissue engineering (cell migration in engineered biomaterials). Improved understanding of the fundamental mechanisms governing interstitial cell migration might lead to interventions that stop invasion processes that culminate in deleterious outcomes and/or that expedite migration to direct endogenous cell-mediated repair and regeneration of joint tissues.
关节内的结缔组织以其致密的细胞外基质和稀疏的细胞组成特征。然而，在受伤或患病时，组织通常会因内源性间充质细胞群体的增殖和迁移以及其他细胞类型（包括免疫细胞）的侵袭而出现细胞涌入。尽管这个过程对于成功的伤口愈合至关重要，但异常的免疫介导的细胞浸润可导致关节的病理性炎症。重要的是，间充质或造血来源的细胞使用不同的迁移模式，因此可能对类似的生物学线索和微环境有不同的反应。此外，肌肉骨骼组织的生理微环境中的细胞迁移与体外迁移有很大的不同。本综述从三个独立但相互依存的角度探讨了纤维结缔组织中细胞迁移的复杂性：生理学（包括影响三维细胞迁移的细胞和细胞外因素）、病理生理学（滑液关节自身免疫性疾病和损伤背景下的细胞迁移）和组织工程（工程生物材料中的细胞迁移）。对控制间质细胞迁移的基本机制的深入了解，可能会导致干预措施的出现，这些干预措施可以阻止导致有害后果的侵袭过程，或者加速迁移，以直接促进内源性细胞介导的关节组织修复和再生。
