VCAM-1 expression on dystrophic muscle vessels 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, α4-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 significantly 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.