Systemic transplantation of c-kit+ cells exerts a therapeutic effect in a model of amyotrophic lateral sclerosis.
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.
Corti
Stefania
S
Dino Ferrari Centre, Department of Neurological Sciences, University of Milan, IRCCS Foundation Ca'Granda, Ospedale Maggiore Policlinico, Milan, Italy.
Nizzardo
Monica
M
Nardini
Martina
M
Donadoni
Chiara
C
Salani
Sabrina
S
Simone
Chiara
C
Falcone
Marianna
M
Riboldi
Giulietta
G
Govoni
Alessandra
A
Bresolin
Nereo
N
Comi
Giacomo P
GP
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
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