title: Adipose-derived stem cell exosomes alleviate pathology of amyotrophic lateral sclerosis in vitro.
abstract: Amyotrophic lateral sclerosis (ALS) is a degenerative disorder that involves the death of motor neurons in the cortex, brain stem, and spinal cord. Adipose-derived stem cells (ADSCs) are considered as a perspective remedy for therapy of neurodegenerative diseases including ALS. Stem cells secrete various factors which can modulate a hostile environment, called paracrine effect. Exosomes are small extracellular vesicles containing cell derived factors and mediate paracrine effect of cells. Thus, exosomes from ADSCs (ADSC-exo) can be a potential candidate of therapeutic effects of stem cells. To investigate the effect of ADSC-exo on the cellular phenotypes of ALS, we used neuronal stem cells (NSCs), which can be differentiated into neuronal cells, isolated from wild type or G93A ALS mice model. ADSC-exo was treated to neuronal cells from G93A ALS mice model. Immunocytochemistry and dot-blot assay result showed that ADSC-exo alleviated aggregation of superoxide dismutase 1 (SOD1). Reduction of cytosolic SOD1 level by ADSC-exo was also confirmed by western blot. Mitochondria display various abnormalities in ALS and the decrease of phospho-CREB and PGC-1α were observed in the G93A cells. ADSC-exo treatment showed normalization of phospho-CREB/CREB ratio and PGC-1α expression level. Our results suggest that ADSC-exo modulates cellular phenotypes of ALS including SOD-1 aggregation and mitochondrial dysfunction, and can be a therapeutic candidate for ALS.
authors.affiliation: Department of Neurology, Seoul National University Hospital, Seoul, South Korea.
authors.forename: Mijung
authors.initials: M
authors.lastname: Lee
authors.affiliation: Department of Neurology, Seoul National University Hospital, Seoul, South Korea.
authors.forename: Jae-Jun
authors.initials: JJ
authors.lastname: Ban
authors.affiliation: Department of Neurology, Seoul National University Hospital, Seoul, South Korea.
authors.forename: Ki Yoon
authors.initials: KY
authors.lastname: Kim
authors.affiliation: Department of Neurology, Seoul National University Hospital, Seoul, South Korea.
authors.forename: Gye Sun
authors.initials: GS
authors.lastname: Jeon
authors.affiliation: Department of Neurology, Seoul National University Hospital, Seoul, South Korea; Neuroscience Research Institute, Seoul National University College of Medicine, Seoul, South Korea. Electronic address: imwooseok@gmail.com.
authors.forename: Wooseok
authors.initials: W
authors.lastname: Im
authors.affiliation: Department of Neurology, Seoul National University Hospital, Seoul, South Korea.
authors.forename: Jung-Joon
authors.initials: JJ
authors.lastname: Sung
authors.affiliation: Department of Neurology, Seoul National University Hospital, Seoul, South Korea; Protein Metabolism Medical Research Center, College of Medicine, Seoul National University, Seoul, South Korea. Electronic address: kimmanho@snu.ac.kr.
authors.forename: Manho
authors.initials: M
authors.lastname: Kim
mesh_terms: D017667:Adipocytes / Q000166:cytology*; D000273:Adipose Tissue / Q000166:cytology; D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism* / Q000628:therapy*; D000818:Animals; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D004195:Disease Models, Animal; D055354:Exosomes / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008928:Mitochondria / Q000378:metabolism; D009046:Motor Neurons / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000378:metabolism; D010641:Phenotype; D013234:Stem Cells / Q000166:cytology*; D000072105:Superoxide Dismutase-1 / Q000378:metabolism
chemical_list: D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; C000606291:Sod1 protein, mouse; D000072105:Superoxide Dismutase-1
keywords: ALS; Adipose-derived stem cell; Exosome; Neuronal stem cell