title: Identification of a putative pathway for the muscle homing of stem cells in a muscular dystrophy model.
abstract: Attempts to repair muscle damage in Duchenne muscular dystrophy (DMD) by transplanting skeletal myoblasts directly into muscles are faced with the problem of the limited migration of these cells in the muscles. The delivery of myogenic stem cells to the sites of muscle lesions via the systemic circulation is a potential alternative approach to treat this disease. Muscle-derived stem cells (MDSCs) were obtained by a MACS(R) multisort method. Clones of MDSCs, which were Sca-1+/CD34-/L-selectin+, were found to adhere firmly to the endothelium of mdx dystrophic muscles after i.v. or i.m. injections. The subpopulation of Sca-1+/CD34- MDSCs expressing L-selectin was called homing MDSCs (HMDSCs). Treatment of HMDSCs with antibodies against L-selectin prevented adhesion to the muscle endothelium. Importantly, we found that vascular endothelium from striate muscle of young mdx mice expresses mucosal addressin cell adhesion molecule-1 (MAdCAM-1), a ligand for L-selectin. Our results showed for the first time that the expression of the adhesion molecule L-selectin is important for muscle homing of MDSCs. This discovery will aid in the improvement of a potential therapy for muscular dystrophy based on the systemic delivery of MDSCs.
authors.affiliation: Department of Neurological Sciences, Stem Cell Laboratory, University of Milan, Padiglione Ponti, Ospedale Policlinico, via Francesco Sforza 35, 20122 Milan, Italy. torrenteyvan@hotmail.com
authors.forename: Yvan
authors.initials: Y
authors.lastname: Torrente
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Camirand
authors.forename: Federica
authors.initials: F
authors.lastname: Pisati
authors.forename: Marzia
authors.initials: M
authors.lastname: Belicchi
authors.forename: Barbara
authors.initials: B
authors.lastname: Rossi
authors.forename: Fabio
authors.initials: F
authors.lastname: Colombo
authors.forename: Mosthapha
authors.initials: M
authors.lastname: El Fahime
authors.forename: Nicolas J
authors.initials: NJ
authors.lastname: Caron
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Issekutz
authors.forename: Gabriela
authors.initials: G
authors.lastname: Constantin
authors.forename: Jacques P
authors.initials: JP
authors.lastname: Tremblay
authors.forename: Nereo
authors.initials: N
authors.lastname: Bresolin
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D018952:Antigens, CD34 / Q000378:metabolism; D000950:Antigens, Ly / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology*; D015815:Cell Adhesion Molecules; D002450:Cell Communication / Q000502:physiology; D002633:Chemotaxis / Q000187:drug effects / Q000502:physiology*; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D005260:Female; D006085:Graft Survival / Q000187:drug effects / Q000502:physiology; D007136:Immunoglobulins / Q000378:metabolism; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D019041:L-Selectin / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D018101:Mice, Inbred mdx; D008822:Mice, Transgenic; D009088:Mucoproteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000098:blood supply / Q000254:growth & development* / Q000503:physiopathology; D009137:Muscular Dystrophy, Animal / Q000378:metabolism* / Q000628:therapy; D020388:Muscular Dystrophy, Duchenne / Q000378:metabolism / Q000628:therapy; D032446:Myoblasts / Q000378:metabolism / Q000637:transplantation*; D033581:Stem Cell Transplantation / Q000379:methods* / Q000639:trends
chemical_list: D000906:Antibodies; D018952:Antigens, CD34; D000950:Antigens, Ly; D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; C074650:Ly6a protein, mouse; C489082:Madcam1 protein, mouse; D008565:Membrane Proteins; D009088:Mucoproteins; D019041:L-Selectin