Human mesenchymal stem cell transplantation extends survival, improves motor performance and decreases neuroinflammation in mouse model of amyotrophic lateral sclerosis.
Amyotrophic lateral sclerosis (ALS) is a lethal disease affecting motoneurons. In familial ALS, patients bear mutations in the superoxide dismutase gene (SOD1). We transplanted human bone marrow mesenchymal stem cells (hMSCs) into the lumbar spinal cord of asymptomatic SOD1(G93A) mice, an experimental model of ALS. hMSCs were found in the spinal cord 10 weeks after, sometimes close to motoneurons and were rarely GFAP- or MAP2-positive. In females, where progression is slower than in males, astrogliosis and microglial activation were reduced and motoneuron counts with the optical fractionator were higher following transplantation. Motor tests (Rotarod, Paw Grip Endurance, neurological examination) were significantly improved in transplanted males. Therefore hMSCs are a good candidate for ALS cell therapy: they can survive and migrate after transplantation in the lumbar spinal cord, where they prevent astrogliosis and microglial activation and delay ALS-related decrease in the number of motoneurons, thus resulting in amelioration of the motor performance.
Vercelli
A
A
Department of Anatomy, Pharmacology and Forensic Medicine, National Institute of Neuroscience, Turin, Italy. alessandro.vercelli@unito.it
Mereuta
O M
OM
Garbossa
D
D
Muraca
G
G
Mareschi
K
K
Rustichelli
D
D
Ferrero
I
I
Mazzini
L
L
Madon
E
E
Fagioli
F
F
D000690:Amyotrophic Lateral Sclerosis / Q000503:physiopathology* / Q000628:therapy*; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D002470:Cell Survival / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D005911:Gliosis / Q000378:metabolism / Q000503:physiopathology / Q000601:surgery; D006801:Humans; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology; D051379:Mice; D017628:Microglia / Q000166:cytology / Q000378:metabolism; D009046:Motor Neurons / Q000473:pathology; D009069:Movement Disorders / Q000209:etiology / Q000503:physiopathology / Q000601:surgery; D009154:Mutation / Q000235:genetics; D009187:Myelitis / Q000503:physiopathology / Q000628:therapy*; D009410:Nerve Degeneration / Q000503:physiopathology / Q000517:prevention & control / Q000601:surgery; D020127:Recovery of Function / Q000502:physiology; D012727:Sex Characteristics; D013116:Spinal Cord / Q000473:pathology / Q000503:physiopathology* / Q000601:surgery*; D013482:Superoxide Dismutase / Q000235:genetics; D000072105:Superoxide Dismutase-1; D015996:Survival Rate; D016896:Treatment Outcome
C000606290:SOD1 protein, human; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1