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. [10.1093/brain/awh273]

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
Primo
;
R. Del Bo
Penultimo
;
G.P. Comi
Ultimo
2004-11

Abstract

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.
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 MED/26 - Neurologia
Article (author)
File in questo prodotto:
Non ci sono file associati a questo prodotto.
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/207214
Citazioni
  • ???jsp.display-item.citation.pmc??? 48
  • Scopus 170
  • ???jsp.display-item.citation.isi??? 155
social impact