Abstract MP29: Skeletal Muscle Satellite Cells Enhance Vascular Growth Through Paracrine Signaling

Abstract

Peripheral arterial disease (PAD) is a major health problem that affects over 200 million people worldwide. Decreased blood flow to the limb muscles leads to ischemia that results in pain, decreased quality of life, and in severe cases amputation. Despite the prevalence and severity of the disease, effective treatment options are still limited. One factor correlated with improved prognosis is the generation of a more robust collateral vessel network. This study hypothesized that skeletal muscle satellite cells, which play a key role in skeletal muscle regeneration, also contribute to vascular regeneration in the setting of ischemia. Specifically, satellite cells are proposed to generate cytokine and growth factors which modulate vascular growth via paracrine signaling. Satellite cells were isolated and cultured for vasculogenic assays include migration co-cultures. Satellite cells encapsulated in alginate were delivered to a hindlimb ischemia model of vascular growth to assess their therapeutic potential in vivo. Gene expression of satellite cells from ischemic tissue was assessed using a microarray. The migration assays demonstrated that satellite cells produce chemokines which increased smooth muscle migration (3.5 fold) and endothelial cell migration (2.8 fold) over control conditions (n = 4, p<0.05) In the hind limb ischemia model, alginate encapsulated satellite cells increased perfusion 17% closer to baseline (68% vs 51%, n = 11, p<0.05) measured via Laser Doppler imaging. Capillary density as measured by Lectin staining increased 1.6 fold and smooth muscle positive vessels increase more than 2 fold (n=6, p<0.05). Finally, Ingenuity pathway analysis of the gene array day suggested that vasculogenic and cell migration pathways were increased. Taken together, these findings demonstrate that satellite cells produce a number of factors that can serve as chemokines in vitro and increase vascular growth in vivo. Further work will explore the mechanisms by which satellite cells exhibit their effects and develop a therapeutic application of satellite cells as a novel treatment for patients with peripheral artery disease.