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

• Published in: Blood Vol. 108; no. 8; pp. 2857 - 2866
• Main Authors: Gavina, Manuela, Belicchi, Marzia, Rossi, Barbara, Ottoboni, Linda, Colombo, Fabio, Meregalli, Mirella, Battistelli, Maurizio, Forzenigo, Laura, Biondetti, Piero, Pisati, Federica, Parolini, Daniele, Farini, Andrea, Issekutz, Andrew C., Bresolin, Nereo, Rustichelli, Franco, Constantin, Gabriela, Torrente, Yvan
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 15.10.2006; The Americain Society of Hematology
• Subjects: AC133 Antigen; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Antigens, CD - metabolism; Applied cell therapy and gene therapy; Biological and medical sciences; Cell Adhesion; Dystrophin - metabolism; Glycoproteins - metabolism; Humans; In Vitro Techniques; Injections, Intra-Arterial; Medical sciences; Mice; Mice, Inbred mdx; Mice, SCID; Muscle, Skeletal - blood supply; Muscle, Skeletal - metabolism; Muscular Dystrophy, Animal - metabolism; Muscular Dystrophy, Animal - therapy; Peptides - metabolism; Peripheral Blood Stem Cell Transplantation; Receptors, Chemokine - metabolism; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Transplantation, Heterologous; Vascular Cell Adhesion Molecule-1 - metabolism; Human; Animal model; Vascular cell adhesion molecule 1; Cell therapy; Stem cell; Hematopoietic cell; Recruitment; Blood cell; Treatment; Blood vessel; Graft; Muscle; Intraarterial administration; Circulatory system; Dystrophy; Myopathy
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2006-04-018564

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 intra-arterial 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.