VCAM-1 expression on dystrophic muscle vessels the has a critical role in the recruitment of human blood-derived CD133+ stem cells after intra-arterial transplantation.

Recently our group demonstrated the myogenic capacity of human CD133 cells isolated from peripheral blood when delivered in vivo through the arterial circulation into the muscle of dystrophic scid/ mdx mice. CD133 stem cells express the adhesion molecules CD44, LFA-1, PSGL-1, 4-integrins, L-selectin, and chemokine receptor CCR7. Moreover these cells adhere in vitro to VCAM-1 spontaneously and after stimulation with CCL19. Importantly, after muscle exercise, we found that the expression of VCAM-1 is strongly up-regulated in dystrophic muscle vessels, whereas the number of rolling and firmly adhered CD133 stem cells signifi cantly increased. Moreover, human dystrophin expression was significantly increased when muscle exercise was performed 24 hours before the intraarterial injection of human CD133 cells. Finally, treatment of exercised dystrophic mice with anti–VCAM-1 antibodies led to a dramatic blockade of CD133 stem cell migration into the dystrophic muscle. Our results show for the first time that the expression of VCAM-1 on dystrophic muscle vessels induced by exercise controls muscle homing of human CD133 stem cells, opening new perspectives for a potential therapy of muscular dystrophy based on the intra-arterial delivery of CD133 stem cells.