Istituto Pasteur-Fondazione Cenci Bolognetti, DAHFMO-Unit of Histology and Medical Embryology, Interuniversity Institute of Myology, Sapienza University of Rome, Rome, Italy.
Methods Mol Biol. 2024;2835:229-247. doi: 10.1007/978-1-0716-3995-5_19.
Skeletal muscle is a postmitotic tissue composed of contractile myofibers that are oriented and connected to different layers of connective tissue. Nevertheless, adult muscle fibers retain the capacity to regenerate in response to damage, activating the classical muscle stem cell compartment, namely, satellite cells (SCs), which are mitotically quiescent cells until required for growth or repair and are localized between the basal lamina and sarcolemma of myofibers. The transition of SCs from the quiescent state toward activation, commitment, and differentiation involves the genetic and epigenetic adaptation to novel biological functions, entailing dynamic changes in the protein expression profile. Interestingly, some of the activities and signaling regulating proliferation, commitment, differentiation, and survival/apoptosis of satellite cells have been also partially recapitulated in vitro, taking advantage of robust markers, reliable techniques, and reproducible protocols. Over the years, different techniques of muscular cell culture have been designed including primary cultures from embryonic or postnatal muscle, myogenic cell line, and three-dimensional (3D) skeletal muscle construct. Typical two-dimensional (2D) muscle cell culture cannot fully recapitulate the complexity of living muscle tissues, restricting their usefulness for physiological studies. The development of functional 3D culture models represents a valid alternative to overcome the limitations of already available in vitro model, increasing our understanding of the roles played by the various cell types and how they interact. In this chapter, the development of bidimensional and three-dimensional cell cultures have been described, improving the technical aspect of satellite cell isolation, the best culture-based conditions for muscle cell growth and differentiation, and the procedures required to develop a three-dimensional skeletal muscle construct.
骨骼肌是一种有丝分裂后组织,由定向排列并连接到不同层结缔组织的收缩肌纤维组成。然而,成年肌肉纤维保留了在受到损伤时再生的能力,激活经典的肌肉干细胞区室,即卫星细胞(SCs),SCs 在需要生长或修复之前处于有丝分裂静止状态,并定位于肌纤维的基底膜和肌膜之间。SCs 从静止状态向激活、定向和分化的转变涉及基因和表观遗传适应新的生物学功能,导致蛋白质表达谱的动态变化。有趣的是,一些调节卫星细胞增殖、定向、分化和存活/凋亡的活性和信号也在体外部分得到了重现,这得益于强大的标记物、可靠的技术和可重复的方案。多年来,已经设计了不同的肌肉细胞培养技术,包括来自胚胎或出生后肌肉的原代培养、成肌细胞系和三维(3D)骨骼肌构建体。典型的二维(2D)肌肉细胞培养不能完全再现活体肌肉组织的复杂性,限制了它们在生理研究中的用途。功能性 3D 培养模型的发展是克服现有体外模型局限性的有效替代方法,可以提高我们对各种细胞类型所起作用以及它们如何相互作用的理解。在本章中,描述了二维和三维细胞培养的发展,改进了卫星细胞分离的技术方面、肌肉细胞生长和分化的最佳基于培养的条件,以及开发三维骨骼肌构建体所需的程序。