title: Neuroprotective Effect of Human Adipose Stem Cell-Derived Extract in Amyotrophic Lateral Sclerosis.
abstract: Amyotrophic lateral sclerosis (ALS) is a devastating human neurodegenerative disease. The precise pathogenic mechanisms of the disease remain uncertain, and as of yet, there is no effective cure. Human adipose stem cells (hASC) can be easily obtained during operative procedures. hASC have a clinically feasible potential to treat neurodegenerative disorders, since cytosolic extract of hASC contain a number of essential neurotrophic factors. In this study, we investigated effects of hASC extract on the SOD1 G93A mouse model of ALS and in vitro test. Administration of hASC extract improved motor function and prolonged the time until symptom onset, rotarod failure, and death in ALS mice. In the hASC extracts group, choline acetyltransferase immunostaining in the ventral horn of the lumbar spinal cord showed a large number of motor neurons, suggesting normal morphology. The neuroprotective effect of hASC extract in ALS mice was also suggested by western blot analysis of spinal cord extract from ALS mice and in vitro test. hASC extract treatment significantly increased expression of p-Akt, p-CREB, and PGC-1α in SOD1 G93A mouse model and in vitro test. Our results indicated that hASC extract reduced apoptotic cell death and recovered mutant SOD1-induced mitochondrial dysfunction. Moreover, hASC extract reduced mitochondrial membrane potential. In conclusion, we have demonstrated, for the first time, that hASC extract exert a potential therapeutic action in the SOD1 G93A mouse model of ALS and in vitro test. These findings suggest that hASC hold promise as a novel therapeutic strategy for treating ALS.
authors.affiliation: Department of Neurology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea.|Biomedical Research Institute, 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 National University College of Medicine, Seoul, South Korea.|Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea.
authors.forename: Wooseok
authors.initials: W
authors.lastname: Im
authors.affiliation: Department of Neurology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Yu-Mi
authors.initials: YM
authors.lastname: Shim
authors.affiliation: Department of Neurology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Mijung
authors.initials: M
authors.lastname: Lee
authors.affiliation: Department of Neurology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Myung-Jin
authors.initials: MJ
authors.lastname: Kim
authors.affiliation: Department of Neurology, Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul, South Korea.
authors.forename: Yoon-Ho
authors.initials: YH
authors.lastname: Hong
authors.affiliation: Wide River Institute of Immunology, Department of Microbiology and Immunology, Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Seung-Yong
authors.initials: SY
authors.lastname: Seong
authors.affiliation: Department of Neurology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea. kimmanho@snu.ac.kr.|Protein Metabolism Medical Research Center, Seoul National University College of Medicine, Seoul, South Korea. kimmanho@snu.ac.kr.
authors.forename: Manho
authors.initials: M
authors.lastname: Kim
authors.affiliation: Department of Neurology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea. jjsaint@snu.ac.kr.
authors.forename: Jung-Joon
authors.initials: JJ
authors.lastname: Sung
mesh_terms: D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism*; D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D002457:Cell Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D002470:Cell Survival; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008822:Mice, Transgenic; D008928:Mitochondria / Q000378:metabolism; D009046:Motor Neurons / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010766:Phosphorylation; D013234:Stem Cells / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000235:genetics; D000072105:Superoxide Dismutase-1; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D002457:Cell Extracts; D017362:Cyclic AMP Response Element-Binding Protein; D018696:Neuroprotective Agents; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D014157:Transcription Factors; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1
keywords: Amyotrophic lateral sclerosis; Human adipose stem cells; Neuroprotection; Paracrine effect; SOD1