title: Systemic transplantation of c-kit+ cells exerts a therapeutic effect in a model of amyotrophic lateral sclerosis.
abstract: Amyotrophic lateral sclerosis (ALS) is a progressive, fatal, neurodegenerative disease characterized by the loss of motor neurons. Motor neuron degeneration is probably both a cell autonomous and a non-autonomous event. Therefore, manipulating the diseased microenvironment via non-neural cell replacement could be a therapeutic strategy. We investigated a cell therapy approach using intravascular injection to transplant a specific population of c-kit(+) stem/progenitor cells from bone marrow into the SOD1G93A mouse model of ALS. Transplanted cells engrafted within the host spinal cord. Cell transplantation significantly prolonged disease duration and lifespan in superoxide dismutase 1 mice, promoted the survival of motor neurons and improved neuromuscular function. Neuroprotection was mediated by multiple effects, in particular by the expression of primary astrocyte glutamate transporter GLT1 and by the non-mutant genome. These findings suggest that this type of somatic cell transplantation strategy merits further investigation as a possible effective therapy for ALS and other neurodegenerative diseases.
authors.affiliation: Dino Ferrari Centre, Department of Neurological Sciences, University of Milan, IRCCS Foundation Ca'Granda, Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Corti
authors.forename: Monica
authors.initials: M
authors.lastname: Nizzardo
authors.forename: Martina
authors.initials: M
authors.lastname: Nardini
authors.forename: Chiara
authors.initials: C
authors.lastname: Donadoni
authors.forename: Sabrina
authors.initials: S
authors.lastname: Salani
authors.forename: Chiara
authors.initials: C
authors.lastname: Simone
authors.forename: Marianna
authors.initials: M
authors.lastname: Falcone
authors.forename: Giulietta
authors.initials: G
authors.lastname: Riboldi
authors.forename: Alessandra
authors.initials: A
authors.lastname: Govoni
authors.forename: Nereo
authors.initials: N
authors.lastname: Bresolin
authors.forename: Giacomo P
authors.initials: GP
authors.lastname: Comi
mesh_terms: D027322:Amino Acid Transport System X-AG / Q000378:metabolism; D000690:Amyotrophic Lateral Sclerosis / Q000201:enzymology / Q000628:therapy*; D000818:Animals; D001681:Biological Assay; D001808:Blood Vessels / Q000473:pathology; D001854:Bone Marrow Cells / Q000166:cytology; D016923:Cell Death; D002469:Cell Separation; D002470:Cell Survival; D018920:Coculture Techniques; D004195:Disease Models, Animal; D005110:Extracellular Space / Q000378:metabolism; D005971:Glutamates / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D051379:Mice; D009046:Motor Neurons / Q000473:pathology; D050505:Mutant Proteins / Q000378:metabolism; D010641:Phenotype; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*; D033581:Stem Cell Transplantation; D013482:Superoxide Dismutase / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D016019:Survival Analysis
chemical_list: D027322:Amino Acid Transport System X-AG; D005971:Glutamates; D036341:Intercellular Signaling Peptides and Proteins; D050505:Mutant Proteins; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D019009:Proto-Oncogene Proteins c-kit