Stromal Cell-derived Factors in Duchenne Muscular Dystrophy

Duchenne muscular dystrophy (DMD) is characterized by increased muscle damage and an abnormal blood flow after muscle contraction leading to a state of functional ischemia. Abundant evidence suggests that endothelial circulating progenitor cells (EPCs) play an important role in mediating vascular and muscle repair mechanisms and that the stromal cell-derived factor (SDF)-1 alpha chemokine is responsible for both progenitor cell mobilization from the bone marrow to peripheral blood and homing to the sites of vascular and tissue injury. Since normal neovascularization is disrupted in DMD pathogenesis and may contribute ultimately to heart failure and sudden death, the aim of the present study is to investigate whether the (SDF)-1 alpha, and EPCs surface receptors in terms of CD34, CD133 and kinase domain receptor (KDR) are involved in DMD pathophysiology. In the present study, peripheral blood concentrations of circulating CD34, CD133, and CD34/ CD 133 progenitor cells were measured by flow cytometry, together with serum levels of (SDF)-1alpha and hypoxia inducible factor (HIF-1alpha.), in 28 DMD patients vs. 20 healthy age and socioeconomic matching controls. Results showed a significant increase in the number of mononuclear cells bearing EPC markers, HIF-1alpha mRNA expression and serum (SDF)-1 alpha, indicating that regeneration is an ongoing process in these patients. However, this regeneration cannot counterbalance the damage induced by dystrophine mutation.