Novel insight into stem cell trafficking in dystrophic muscles.
Recently published reports have described possible cellular therapy approaches to regenerate muscle tissues using arterial route delivery. However, the kinetic of distribution of these migratory stem cells within injected animal muscular dystrophy models is unknown. Using living X-ray computed microtomography, we established that intra-arterially injected stem cells traffic to multiple muscle tissues for several hours until their migration within dystrophic muscles. Injected stem cells express multiple traffic molecules, including VLA-4, LFA-1, CD44, and the chemokine receptor CXCR4, which are likely to direct these cells into dystrophic muscles. In fact, the majority of intra-arterially injected stem cells access the muscle tissues not immediately after the injection, but after several rounds of recirculation. We set up a new, living, 3D-imaging approach, which appears to be an important way to investigate the kinetic of distribution of systemically injected stem cells within dystrophic muscle tissues, thereby providing supportive data for future clinical applications.
Stem Cell Laboratory, Department of Neurological Sciences, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico di Milano, Centro Dino Ferrari, Università di Milano, Milano, Italy.
Andrea
A
Farini
Chiara
C
Villa
Adrian
A
Manescu
Fabrizio
F
Fiori
Alessandra
A
Giuliani
Paola
P
Razini
Clementina
C
Sitzia
Giulia
G
Del Fraro
Marzia
M
Belicchi
Mirella
M
Meregalli
Franco
F
Rustichelli
Yvan
Y
Torrente
D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000097:blood / Q000737:chemistry; D002478:Cells, Cultured; D003911:Dextrans / Q000737:chemistry / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D005121:Extremities / Q000000981:diagnostic imaging; D006023:Glycoproteins / Q000097:blood / Q000737:chemistry; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000378:metabolism; D058185:Magnetite Nanoparticles / Q000737:chemistry; D051379:Mice; D016513:Mice, SCID; D009136:Muscular Dystrophies / Q000601:surgery*; D010455:Peptides / Q000097:blood / Q000737:chemistry; D060888:Real-Time Polymerase Chain Reaction; D057905:Stem Cell Research; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000737:chemistry / Q000166:cytology*; D014018:Tissue Distribution; D055114:X-Ray Microtomography / Q000379:methods*
D000071916:AC133 Antigen; D015703:Antigens, CD; D003911:Dextrans; D006023:Glycoproteins; D058185:Magnetite Nanoparticles; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse; C065507:ferumoxides