Cellular interplay in skeletal muscle regeneration and wasting: insights from animal models

Abstract

Skeletal muscle wasting, whether related to physiological ageing, muscle disuse or to an underlying chronic disease, is a key determinant to quality of life and mortality. However, cellular basis responsible for increased catabolism in myocytes often remains unclear. Although myocytes represent the vast majority of skeletal muscle cellular population, they are surrounded by numerous cells with various functions. Animal models, mostly rodents, can help to decipher the mechanisms behind this highly dynamic process, by allowing access to every muscle as well as time-course studies. Satellite cells (SCs) play a crucial role in muscle regeneration, within a niche also composed of fibroblasts and vascular and immune cells. Their proliferation and differentiation is altered in several models of muscle wasting such as cancer, chronic kidney disease or chronic obstructive pulmonary disease (COPD). Fibro-adipogenic progenitor cells are also responsible for functional muscle growth and repair and are associated in disease to muscle fibrosis such as in chronic kidney disease. Other cells have recently proven to have direct myogenic potential, such as pericytes. Outside their role in angiogenesis, endothelial cells and pericytes also participate to healthy muscle homoeostasis by promoting SC pool maintenance (so-called myogenesis-angiogenesis coupling). Their role in chronic diseases muscle wasting has been less studied. Immune cells are pivotal for muscle repair after injury: Macrophages undergo a transition from the M1 to the M2 state along with the transition between the inflammatory and resolutive phase of muscle repair. T regulatory lymphocytes promote and regulate this transition and are also able to activate SC proliferation and differentiation. Neural cells such as terminal Schwann cells, motor neurons and kranocytes are notably implicated in age-related sarcopenia. Last, newly identified cells in skeletal muscle, such as telocytes or interstitial tenocytes could play a role in tissular homoeostasis. We also put a special focus on cellular alterations occurring in COPD, a chronic and highly prevalent respiratory disease mainly linked to tobacco smoke exposure, where muscle wasting is strongly associated with increased mortality, and discuss the pros and cons of animal models versus human studies in this context. Finally, we discuss resident cells metabolism and present future promising leads for research, including the use of muscle organoids.

Ultrastructural characteristics and morphological relationships of cardiomyocytes and telocytes in the myocardium of the bullfrog (Rana catesbeiana)

“…In addition, the Tps and the muscle satellite cells established heterocellular structural connections by tight junctions. It has been suggested that TCs cross‐talk with satellite cells by direct contacts (Henrot et al., 2023). Therefore, TCs may play a role in tissue regeneration and homoeostasis of the myocardium by regulating satellite cells.…”

“…Muscle satellite cells are resident stem cells located beneath the basal lamina of myofibres. They are essential for muscle tissue regeneration, by proliferating and differentiating into myotubes, which later fuse and give rise to functional myofibres (Henrot et al., 2023; Morgan & Partridge, 2003). TCs have been identified in the vicinity of satellite cells (Mitrofanova et al., 2018).…”

Telocytes and inflammation: A review

“…[47] In skin and skeletal muscle, TCs can integrate skeletal muscle fiber regulation and affect the regeneration of skin and skeletal muscle. [25,48,49]…”

“…TCs are widespread in a variety of tissues and organs, such as cardiac tissues, [5,6] vessels, [7] the trachea and lungs, [8,9] gallbladder, [10] liver, [11] Intestinal tissues, [12] duodenum, [13] colon, [14] and spleen, [15] and they are also found in the male genitals including the testis, [16] and epididymis, [17] as well as the female genital organs and the uterus, [18,19] oviduct, [20] and placenta. [21] In addition, TCs are also found in the pleura, [22] skin, [1] parotid glands, [23] skeletal muscle, [24,25] and epithelium. [26] After more than 20 years of exploration, TCs have been shown to exist in almost all tissues and organs.…”

Main Pathogenic Mechanisms and Recent Advances in COPD Peripheral Skeletal Muscle Wasting

“…On a semantic point of view, different terms can be found in the literature, which should be distinguished from each other. Sarcopenia is a specific form of muscle loss diagnosed through a loss of muscle force and mass and is associated to several conditions other than COPD, primarily aging [ 8 ]. Muscle atrophy or wasting is a general term defining a reduction in the size of the muscle fibers, caused by an increased catabolism, whereas muscle dysfunction rather refers to a loss of force.…”