Intravenous Mesenchymal Stem Cells Improve Survival and Motor Function in Experimental Amyotrophic Lateral Sclerosis

摘要: Despite some advances in the understanding of amyotrophic lateral sclerosis (ALS) pathogenesis, significant achievements treating this disease are still lacking. Mesenchymal stromal (stem) cells (MSCs) have been shown to be effective several models neurological disease. To determine effects intravenous injection MSCs an ALS mouse model during symptomatic stage disease, (1 × 106) were intravenously injected mice expressing human superoxide dismutase 1 (SOD1) carrying G93A mutation (SOD1/G93A) presenting with experimental ALS. Survival, motor abilities, histology, oxidative stress markers and [3H]d-aspartate release spinal cord investigated. MSC SOD1/G93A improved survival functions compared saline-injected controls. Injected scantly home central nervous system poorly engraft. We observed a reduced accumulation ubiquitin agglomerates activated astrocytes microglia MSC-treated mice, no changes number choline acetyltransferase- glutamate transporter type 1-positive cells. administration turned around upregulation metallothionein mRNA expression activity antioxidant enzyme glutathione S-transferase, both associated progression. Last, we that reverted spontaneous stimulus-evoked neuronal (3H)d-aspartate, marker endogenous glutamate, which is upregulated mice. These findings suggest significantly improves clinical outcome pathological scores mutant thus providing rationale for their exploitation treatment