Emerging Development of Microfluidics-Based Approaches to Improve Studies of Muscle Cell Migration

Cell migration is an essential process in which cells move from one location to another with different modes, including mesenchymal, amoeboid, or collective movements. Migration occurs during development and in the maintenance of multicellular organisms for purposes of wound healing, tissue regeneration, and immune and pathophysiological responses. Cells in all three types of muscle: cardiac, smooth, and skeletal, are subject to and undergo migration, both general and adapted for tissue-specific needs. Cardiac cell migration is mediated by vascular endothelial growth factor (VEGF) through expression of VEGF receptors; it is not clear how cardiac cells migrate into a region of damage after infarction. In skeletal muscle, satellite cells, with dual roles as muscle precursors and self-renewing multipotent adult stem or stromal cells, are resident on muscle fibers and normally mitotically inactive. Their activation and subsequent migration critically mediate skeletal muscle repair. Nitric oxide and hepatocyte growth factor are important signaling factors and the only two chemical factors that activate satellite cells. Both induce satellite cell motility on fibers in culture and into a region of muscle damage in vivo. By comparison, vascular smooth muscle cells migrate in response to vascular injury, during the normal process of angiogenesis, and in the pathological process of atherogenesis and vascular thickening. Microfluidic devices are advantageous in their capability to control cellular microenvironments and thus offer a valuable approach for the quantitative study of cell migration in vitro: devices can be designed to incorporate conditions that mimic what is known of normal physiology and control of microenvironmental changes can model particular situations. In this direction, there is increasing interest in developing innovative microfluidic devices to enable investigation of the migration behavior of different muscle cells. The mechanisms of muscle cell migration and their physiological roles are discussed in context of the emerging development of microfluidics-based approaches to advance studies of muscle cell migration and highlight their potential applications. Impact Statement The essential interactions between and among cells in the three types of muscle tissue in development, wound healing, and regeneration of tissues, are underpinned by the ability of cardiac, smooth, and skeletal muscle cells to migrate in maintaining functional capacity after pathologies such as myocardial infarction, tissue grafting, and traumatic and postsurgical injury. Microfluidics-based devices now offer significant enhancement over conventional approaches to studying cell chemotaxis and haptotaxis that are inherent in migration. Advances in experimental approaches to muscle cell movement and tissue formation will contribute to innovations in tissue engineering for patching wound repair and muscle tissue replacement.