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Blood First Edition Paper, prepublished online October 5, 2006; DOI 10.1182/blood-2006-04-018564.
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Submitted April 24, 2006
Accepted June 15, 2006
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
Manuela Gavina, Marzia Belicchi, Barbara Rossi, Linda Ottoboni, Fabio Colombo, Mirella Meregalli, Maurizio Battistelli, Laura Forzenigo, Piero Biondetti, Federica Pisati, Daniele Parolini, Andrea Farini, Andrew C Issekutz, Nereo Bresolin, Franco Rustichelli, Gabriela Constantin, and Yvan Torrente*
Stem cell Laboratory, Dept. of Neurological Science, Fondazione IRCCS, University of Milan, Italy
Department of Pathology, Division of General Pathology, University of Verona, Strada le Grazie,Italy
Fondazione IRCCS Ospedale Maggiore Policlinico, Institute of Nuclear Medecine, Milan, Italy
Radiology Unit, Fondazione IRCCS Ospedale Maggiore Policlinico of Milan, Italy
Department of Pediatrics, Pathology and Microbiology-Immunology, Dalhousie University,Halifax,Canada
Department of Sciences Applied to Complex Systems, Polytechnic University of Marche, Italy
* Corresponding author; email: yvan.torrente{at}unimi.it.
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. The CD133+ stem
cells express the adhesion molecules CD44, LFA-1, PSGL-
1,  4integrins and L-selectin, and chemokine receptor
CCR7. Moreover these cells adhere in vitro to VCAM-1
spontaneously and also after stimulation with CCL19.
Importantly, after muscle exercise we found that
expression of VCAM-1 is strongly upregulated in
dystrophic muscle vessels while 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 cells 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.
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