Human muscle stem cell physiology: Characterization, regulation and function.

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BACKGROUND: The processes that govern muscle adaptation and repair are highly complex and involve interactions between multiple organs, tissues, cells, sub cellular organelles and a host of coordinated molecular signaling events. Many of these interactions/events remain to be elucidated. It is not yet clear how satellite cells interact with their environment to promote adaptation/repair or whether specific relationships between satellite cells and other structures, such as capillaries, are important in regulating satellite cell function. Furthermore, although satellite cells are considered to be the primary stem cell population in skeletal muscle there is evidence in rodents suggesting the presence of other stem/progenitor populations that have never even been described in human skeletal muscle, but may nonetheless be important in supporting skeletal muscle growth and adaptation. OBJECTIVES: 1. To characterize the relationships between muscle satellite cells, muscle fiber capillaries and skeletal muscle adaptation/repair. 2. To identify and characterize a novel stem cell population in skeletal muscle at rest and following acute and chronic exercise. PW1 interstitial cells (PICS) has been described in rodents and are anatomically and functionally distinct from satellite cells but have been shown to participate in muscle regeneration as efficiently as satellite cells. For the first time, we recently identified PICS in human skeletal muscle. SCIENTIFIC APPROACH: Using stimulus response studies in healthy humans and specialized techniques and study designs we will examine the relationship between satellite cells and muscle capillaries. We believe those with the highest levels of capillarization will experience the most robust acute satellite cell response and will therefore, be best positioned for optimal adaptation. We will also characterize the PICS population in human skeletal muscle and we will examine the acute responses to single bouts of damaging exercise as well as the chronic responses to exercise-training paradigms to fully characterize the PICS population at rest, following acute exercise and following training. SIGNIFICANCE: These objectives will continue to build upon the progress we have made and generate new knowledge of how human skeletal muscle can repair/adapt/grow in response to a specific stimulus.