Novel insight into stem cell trafficking in dystrophic muscles

Andrea Farini,^1,* Chiara Villa,^1,* Adrian Manescu,² Fabrizio Fiori,² Alessandra Giuliani,² Paola Razini,¹ Clementina Sitzia,¹ Giulia Del Fraro,¹ Marzia Belicchi,¹ Mirella Meregalli,¹ Franco Rustichelli,² Yvan Torrente<sup>1

1</sup>Stem Cell Laboratory, Department of Neurological Sciences, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico di Milano, Centro Dino Ferrari, Università di Milano, Milano, Italy; ²Università Politecnica delle Marche, Di.S.C.O. - Sezione di Biologia, Biochimica e Fisica Ancona, Italy

^*These authors contributed equally to this paper

Abstract: 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.

Keywords: iron nanoparticles, micro-CT, CD133⁺ stem cells, dystrophic muscles