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Neuroprotective Effect of Human Adipose Stem Cell-Derived Extract in Amyotrophic Lateral Sclerosis

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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.

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Abbreviations

ALS:

Amyotrophic lateral sclerosis

hASC:

Human adipose stem cells

SOD1:

Superoxide dismutase-1

ChAT:

Choline acetyltransferase

HD:

Huntington’s disease

MMP:

Membrane potential

MSCs:

Mesenchymal stem cells

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Acknowledgments

This study was supported by Grants from the Korea Healthcare Technology R&D project, Ministry of health and Welfare, Republic of Korea (HI14C3347).

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    Authors and Affiliations

    1. Department of Neurology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea

      Gye Sun Jeon, Wooseok Im, Yu-Mi Shim, Mijung Lee, Myung-Jin Kim, Manho Kim & Jung-Joon Sung

    2. Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea

      Gye Sun Jeon & Wooseok Im

    3. Department of Neurology, Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul, South Korea

      Yoon-Ho Hong

    4. Wide River Institute of Immunology, Department of Microbiology and Immunology, Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, South Korea

      Seung-Yong Seong

    5. Protein Metabolism Medical Research Center, Seoul National University College of Medicine, Seoul, South Korea

      Manho Kim

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    Correspondence to Manho Kim or Jung-Joon Sung.

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    Gye Sun Jeon and Wooseok Im have contributed equally to this work.

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    Figure S1

    Comparison of growth factors between hASC and hASC extract. BDNF, VEGF, PDGF-1, IGF-1, HGF-α, FGF-2 were investigated in hASC or hASC extract by western blot. The results showed that both groups contained various growth factors similarly (BDNF, Brain-derived neurotrophic factor; VEGF, Vascular endothelial growth factor; PDGF-1, Platelet-derived growth factor-1; IGF-1, Insulin-like growth factors-1; HGF-α, Hepatocyte growth factor-α; FGF-2, Fibroblast growth factor-2) (JPEG 273 kb)

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    Jeon, G.S., Im, W., Shim, YM. et al. Neuroprotective Effect of Human Adipose Stem Cell-Derived Extract in Amyotrophic Lateral Sclerosis. Neurochem Res 41, 913–923 (2016). https://doi.org/10.1007/s11064-015-1774-z

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