Skeletal muscle is a highly adaptable tissue with well-known sensitivities to environmental cues such as growth factors, cytokines, nutrients and mechanical loading. Moreover, adult skeletal muscle exhibits great plasticity and has the unique capacity to regenerate after injury, due to satellite cells, the muscle stem cells. Satellite cells, and their progeny, the myogenic precursor cells, must develop proper interactions with their direct environment to ensure muscle regeneration and replenishment of the stem cell pool. The aim of our research is to understand the role of the environment (non-myogenic cells and molecular structures) in the regulation of skeletal muscle regeneration. Myogenic cell environment includes inflammatory cells and particularly macrophages, vessel cells (endothelial and peri-endothelial cells) and interstitial cells. We aim at understanding the interactions between myogenic cells and their environment in various physiological and pathological situations.
Muscle stem cell neighboring (B. Chazaud)
Skeletal muscle regeneration is associated with the presence of macrophages. Two main types of macrophages are present during skeletal muscle regeneration. Soon after injury, inflammatory monocytes enter into the damaged muscle (1) and these inflammatory macrophages stimulate the proliferation of muscle stem cells (2). Upon efferocytosis, which is the engulfment of cell and tissue debris, they switch their phenotype into anti-inflammatory/repair macrophages (3), that sustain myogenic differentiation (4) fusion and myofiber growth (5), as well as angiogenesis and matrix remodeling, until the return to homeostasis (6). Macrophages can be considered as a major actor of the regenerative niche of myogenic cells that helps the sequential steps of skeletal muscle regeneration. An important aspect in macrophage functions is their dynamic during tissue repair, with a crucial moment when the inflammatory phase ends to start the repair process, that is the resolution of inflammation.
Neuromuscular electrical stimulation training to fight cachexia (J. Gondin)
Cachexia is a common consequence of many chronic diseases including sepsis and cancer. This loss of skeletal muscle mass ultimately results in increased morbidity and mortality. Moreover, treatments, sedation and/or prolonged unloading may further increase muscle deconditioning. On that basis, the development of countermeasures to prevent or attenuate the loss of skeletal muscle mass is of utmost importance for both patients. Our aim is to investigate whether and to what extent NeuroMuscular Electrical Stimulation (NMES) is a promising therapy for increasing force production and promoting muscle growth in preclinical models of cachexia. The program aims at establishing rigorous protocols to exploit the benefit of NMES on muscle function and at identifying the cellular and molecular events underlying those beneficial effects.
