Synchrotron radiation microtomography for the ex vivo and in vivo investigation of stem cell homing in dystrophic muscle tissue.
Duchenne Muscular Dystrophy (DMD) is a severe form of muscular dystrophy, characterized by a rapid progression of muscle degeneration leading to loss of ambulation and death, often within the late teens and rarely exceeding 30. DMD affects almost exclusively male individuals (approximately 1 out of 3500 worldwide), during the first years of their life (first symptoms appear at the age of 3--5); females can be carriers and may be afflicted if the father is afflicted and the mother is also a carrier. DMD is due to an alteration of X chromosome, causing the lack of production of the dystrophin protein. The absence of dystrophin permits excess calcium to penetrate the sarcolemma (cell membrane); as a consequence, in a complex and not completely understood cascading process involving several pathways, severe damages in the sarcolemma are caused, eventually resulting in cell death. Muscle fibers lacerate during contraction, undergo necrosis and are ultimately replaced by adipose and connective tissue. Presently there is no known cure for DMD. Nevertheless, recent stem-cell research is showing promising vectors that may replace damaged muscle tissue. Understanding the muscle homing of stem cells can improve potential therapies based on systemic delivery. To this end, iron oxide nanoparticle-labeled stem cells were injected into scid/mdx mice, and both $ex vivo$ and $in vivo$ measurements were carried out at ESRF - Grenoble. Our studies showed that the distribution of intra-arterially delivered CD133+ stem cells can be visualized by $\mu$-CT both in muscle biopsies and in living murine models, providing biological insights into the early processes of stem cell homing. Very recently, these experimental results were used as a base for the newly approved COST project BIONECA, connecting physical sciences with regenerative cardiology and neurology.