Amyotrophic lateral sclerosis (ALS) is a progressive, lethal neurodegenerative disease without any effective therapy. To evaluate the potential of wild-type bone marrow (BM)-derived stem cells to modify the ALS phenotype, we generated BM chimeric Cu/Zn superoxide dismutase (SOD1) mice by transplantation of BM cells derived from mice expressing green fluorescent protein (GFP) in all tissues and from Thy1-YFP mice that express a spectral variant of GFP (yellow fluorescent protein) in neurons only. In the recipient cerebral cortex, we observed rare GFP+ and YFP+ neurons, which were probably generated by cell fusion, as demonstrated by fluorescence in situ hybridization (FISH) analysis, suggesting that this phenomenon is not limited to Purkinje cells. GFP-positive microglial cells were extensively present in both the brain and spinal cord of the affected animals. Completely differentiated and immature GFP+ myofibres were also present in the heart and skeletal muscles of SOD1 mice, confirming that BM cells can participate in striated muscle tissue regeneration. Moreover, wild-type BM chimeric SOD1 mice showed a significantly delayed disease onset and an increased life span, probably due to a positive 'non-neuronal environmental' effect rather than to neuronogenesis. This improvement in SOD1-G93A mouse survival is comparable with that previously obtained using some safer pharmacological agents. BM transplantation-related complications in humans preclude its clinical application for ALS treatment. However, our data suggest that further studies aimed at improving the degree of tissue chimerism by BM-derived cells may provide valuable insights into strategies to slow ALS progression.
Wild-type bone marrow cells ameliorate the phenotype of SOD1-G93A ALS mice and contribute to CNS, heart and skeletal muscle tissues / S.P. Corti, F. Locatelli, C. Donadoni, M. Guglieri, D. Papadimitriou, S. Strazzer, R. Del Bo, G.P. Comi. - In: BRAIN. - ISSN 0006-8950. - 127:Pt 11(2004 Nov), pp. 2518-2532.
|Titolo:||Wild-type bone marrow cells ameliorate the phenotype of SOD1-G93A ALS mice and contribute to CNS, heart and skeletal muscle tissues|
CORTI, STEFANIA PAOLA (Primo)
DEL BO, ROBERTO (Penultimo)
COMI, GIACOMO PIETRO (Ultimo)
|Parole Chiave:||Superoxide Dismutase ; Animals ; Spinal Cord ; Transplantation Chimera ; In Situ Hybridization, Fluorescence ; Cell Differentiation ; Mice ; Mice, Transgenic ; Muscle, Skeletal ; Cerebral Cortex ; Phenotype ; Amyotrophic Lateral Sclerosis ; Neurons ; Bone Marrow Transplantation ; Survival Analysis ; Myocardium|
|Settore Scientifico Disciplinare:||Settore MED/26 - Neurologia|
|Data di pubblicazione:||nov-2004|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1093/brain/awh273|
|Appare nelle tipologie:||01 - Articolo su periodico|