title: 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.
abstract: 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, alpha4-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.
authors.affiliation: Stem Cell Laboratory, Department of Neurological Sciences, IRCCS, Centro Dino Ferrari, University of Milan, Ospedale Maggiore Policlinico, via Francesco Sforza 35, 20122 Milan, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Gavina
authors.forename: Marzia
authors.initials: M
authors.lastname: Belicchi
authors.forename: Barbara
authors.initials: B
authors.lastname: Rossi
authors.forename: Linda
authors.initials: L
authors.lastname: Ottoboni
authors.forename: Fabio
authors.initials: F
authors.lastname: Colombo
authors.forename: Mirella
authors.initials: M
authors.lastname: Meregalli
authors.forename: Maurizio
authors.initials: M
authors.lastname: Battistelli
authors.forename: Laura
authors.initials: L
authors.lastname: Forzenigo
authors.forename: Piero
authors.initials: P
authors.lastname: Biondetti
authors.forename: Federica
authors.initials: F
authors.lastname: Pisati
authors.forename: Daniele
authors.initials: D
authors.lastname: Parolini
authors.forename: Andrea
authors.initials: A
authors.lastname: Farini
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Issekutz
authors.forename: Nereo
authors.initials: N
authors.lastname: Bresolin
authors.forename: Franco
authors.initials: F
authors.lastname: Rustichelli
authors.forename: Gabriela
authors.initials: G
authors.lastname: Constantin
authors.forename: Yvan
authors.initials: Y
authors.lastname: Torrente
mesh_terms: D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D002448:Cell Adhesion; D016189:Dystrophin / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007269:Injections, Intra-Arterial; D051379:Mice; D018101:Mice, Inbred mdx; D016513:Mice, SCID; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000378:metabolism*; D009137:Muscular Dystrophy, Animal / Q000378:metabolism* / Q000628:therapy*; D010455:Peptides / Q000378:metabolism; D036102:Peripheral Blood Stem Cell Transplantation; D019707:Receptors, Chemokine / Q000378:metabolism; D014183:Transplantation, Heterologous; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D016189:Dystrophin; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse; D019707:Receptors, Chemokine; D019010:Vascular Cell Adhesion Molecule-1