School of Biomedical Engineering, 2222 Health Sciences Mall, The University of British Columbia, Vancouver, British Columbia, V6T 1Z3, Canada.
School of Biomedical Engineering, 2222 Health Sciences Mall, The University of British Columbia, Vancouver, British Columbia, V6T 1Z3, Canada.
Exp Cell Res. 2022 Jan 1;410(1):112947. doi: 10.1016/j.yexcr.2021.112947. Epub 2021 Nov 22.
While the majority of healthy skeletal muscle consists of multinucleated syncytial repetitive contractile myofibers, repaired by skeletal muscle stem cells when damaged, the maintenance of muscle function also requires a range of tissue-resident stromal populations. In fact, the careful orchestration of damage response processes upon muscle injury relies heavily on stromal cell contribution for effective repair. The two main types of muscle-resident stromal cells are fibro/adipogenic progenitors and mural cells. The latter is comprised of pericytes and vascular smooth muscle cells. Recent publications identifying common markers for stromal cell populations have allowed investigating population dynamics throughout the regenerative process at a higher resolution. Mounting evidence now suggests that subpopulations with distinct roles may exist among stromal cells. In various degenerative muscle wasting conditions, critical cross-talk and spatial signalling amongst various cell populations become dysregulated. This can result in the failure to curb pathological fibro/adipogenic progenitor proliferation and propensity for laying down excessive extracellular matrix, which in turn leads to fibrotic infiltration, reduced contractile units and gradual decline in muscle function. Restoration of physiologically appropriate stromal cell function is therefore just as crucial for therapeutic targeting as the homeostatic maintenance of muscle function.
虽然大多数健康的骨骼肌由多核合胞重复收缩的肌纤维组成，当受损时由骨骼肌干细胞修复，但肌肉功能的维持还需要一系列组织驻留的基质细胞群体。事实上，肌肉损伤后的损伤反应过程的精心协调在很大程度上依赖于基质细胞的贡献以实现有效的修复。两种主要的肌肉驻留基质细胞类型是成纤维/脂肪祖细胞和成肌细胞。后者由周细胞和血管平滑肌细胞组成。最近的出版物确定了基质细胞群体的共同标记物，从而可以在更高的分辨率下研究整个再生过程中的群体动态。越来越多的证据表明，基质细胞中可能存在具有不同作用的亚群。在各种退行性肌肉消耗条件下，各种细胞群体之间的关键串扰和空间信号传导会失调。这可能导致病理性成纤维/脂肪祖细胞增殖和过度细胞外基质沉积的倾向无法得到抑制，进而导致纤维化浸润、收缩单位减少以及肌肉功能逐渐下降。因此，恢复生理上适当的基质细胞功能对于治疗靶点与维持肌肉功能的动态平衡同样重要。
