Abstract 649: Skeletal Muscle Satellite Cells Play a Role in Regulating Angiogenesis and Arteriogenesis

Abstract

Satellite cells are myogenic stem cells that play a critical role in skeletal muscle repair by proliferating and differentiating into myoblasts to repair muscle fibers. However, their role in reestablishing vascular supply following injury is not well defined. We hypothesized that satellite cells promote vascular growth through paracrine signaling induced following muscle injury or ischemic damage from diseases such as peripheral artery disease. We used a murine model of hind limb ischemia and found that satellite cells increased 3.4 fold (p<0.01) in response to this ischemic insult. We used a co-culture system to determine that satellite cells led to a 3.5 fold and 2.8 fold increase in smooth muscle and endothelial cell migration (p<0.0001). These results demonstrate the satellite cells produce paracrine factors which drive cell migration required for both angiogenesis and arteriogenesis. To test the potential therapeutic capability, alginate encapsulated satellite cells were delivered in the hind limb ischemic model. We found the encapsulated cells were viable for up to 2 weeks and mice that received satellite cells had significantly increased perfusion (28%, p<0.05) at 2 weeks as measured by Laser Doppler imaging and a 1.9 fold (p<0.5) increase in capillaries and small vessels measured by histological staining. To examine the role of satellite cells in a physiological setting and determine if they are critical to robust recovery in our model, we used a Cre-Lox system in which recombination results in the production of diphtheria toxin a (DTA) to deplete Pax7 specific cells. Mice which lacked satellite cells had decreased perfusion by Laser Doppler imaging (p<0.05) and capillary density compared animals with intact satellite cells. A cytokine array and genomics analysis show that several factors related to angiogenesis and cell migration are upregulated in satellite cells in response to ischemia. In conclusion, we have found that satellite cells proliferate in response to ischemia, produce factors that drive cell migration, and their delivery or depletion affect vascular growth in vitro. We believe that our studies show that satellite cells play an important role vascular growth and are a novel potential therapy for peripheral artery disease.