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Aging impairs the ability of satellite cells to induce angiogenesis in vitro

During aging, muscle mass declines in man and experimental animals, and muscles from aged animals have a reduced capacity for regeneration. This defect is associated with inadequate angiogenesis resulting in delayed muscle vascularization and coincides with a decline in the number and proliferative ability of myogenic stem cells (satellite cells). To determine if satellite cells participate in angiogenic processes and are responsible for the age‐related decline in revascularization of regenerating muscle, we developed an in vitro co‐culture model composed of adult (9 mo) or aged (24 mo) rat satellite cells (RSC) and microvascular fragments (MF). In this system, MF are isolated from rat epidydimal fat pad by collagenase digestion and differential selection through various size screens. Isolated MF are resuspended in collagen gel and plated over a RSC monolayer culture. MF cultured in the presence of adult RSC exhibit greater indices of angiogenesis (endothelial cell sprouting, tubule formation and extensive branching) than MF cultured with aged RSC. To determine if the greater degree of angiogenesis we observed in the co‐culture setting was due to soluble factors produced by RSC or direct participation of cells, we cultured MF in the presence of RSC conditioned medium (CM). Adult RSC CM stimulated MF growth to a greater degree than aged RSC CM suggesting that aging impacts the ability of RSC to secrete soluble‐acting growth factor(s). These observations suggest that the promotion of angiogenesis by RSC is diminished with aging.