内源性骨骼肌发育,再生,病理学是极其复杂的过程,受局部和系统性因素的影响。了解这些机制如何发挥作用对于基础生物学和开发遗传性疾病的治疗干预措施至关重要,但也包括肌肉减少症和体积肌肉损失。离体骨骼肌模型的范围包括单独或共培养的卫星干细胞衍生的成肌细胞的二维和三维原代培养物。单个肌肉肌纤维,成肌束,和整个组织。一起,这些系统提供了获得干细胞行为机制见解的机会,细胞-细胞相互作用,在简化的系统中成熟的肌肉功能,没有混淆变量。这里,我们强调使用体外原代细胞和离体骨骼肌模型的最新进展(在过去5年中发表),总结新的见解,工具,数据集,和他们提供的筛选方法。最后,我们强调了骨骼肌知识指数级进步的机会,具有时空分辨率,通过计算机建模指导肌肉生物学和生理学的研究,并实施高含量的细胞生物学系统和离体生理学平台。
Endogenous skeletal muscle development, regeneration, and pathology are extremely complex processes, influenced by local and systemic factors. Unpinning how these mechanisms function is crucial for fundamental biology and to develop therapeutic interventions for genetic disorders, but also conditions like sarcopenia and volumetric muscle loss. Ex vivo skeletal muscle models range from two- and three-dimensional primary cultures of satellite stem cell-derived myoblasts grown alone or in co-culture, to single muscle myofibers, myobundles, and whole tissues. Together, these systems provide the opportunity to gain mechanistic insights of stem cell behavior, cell-cell interactions, and mature muscle function in simplified systems, without confounding variables. Here, we highlight recent advances (published in the last 5 years) using in vitro primary cells and ex vivo skeletal muscle models, and summarize the new insights, tools, datasets, and screening methods they have provided. Finally, we highlight the opportunity for exponential advance of skeletal muscle knowledge, with spatiotemporal resolution, that is offered by guiding the
study of muscle biology and physiology with in silico modelling and implementing high-content cell biology systems and ex vivo physiology platforms.