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Neurochemical Research

, Volume 41, Issue 4, pp 913–923 | Cite as

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

  • Gye Sun Jeon
  • Wooseok Im
  • Yu-Mi Shim
  • Mijung Lee
  • Myung-Jin Kim
  • Yoon-Ho Hong
  • Seung-Yong Seong
  • Manho KimEmail author
  • Jung-Joon SungEmail author
Original Paper

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.

Keywords

Human adipose stem cells SOD1 Amyotrophic lateral sclerosis Neuroprotection Paracrine effect 

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

Notes

Acknowledgments

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

Supplementary material

11064_2015_1774_MOESM1_ESM.jpg (274 kb)
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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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Gye Sun Jeon
    • 1
    • 2
  • Wooseok Im
    • 1
    • 2
  • Yu-Mi Shim
    • 1
  • Mijung Lee
    • 1
  • Myung-Jin Kim
    • 1
  • Yoon-Ho Hong
    • 3
  • Seung-Yong Seong
    • 4
  • Manho Kim
    • 1
    • 5
    Email author
  • Jung-Joon Sung
    • 1
    Email author
  1. 1.Department of Neurology, Seoul National University HospitalSeoul National University College of MedicineSeoulSouth Korea
  2. 2.Biomedical Research InstituteSeoul National University HospitalSeoulSouth Korea
  3. 3.Department of NeurologySeoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical CenterSeoulSouth Korea
  4. 4.Wide River Institute of Immunology, Department of Microbiology and Immunology, Department of Biomedical SciencesSeoul National University College of MedicineSeoulSouth Korea
  5. 5.Protein Metabolism Medical Research Center Seoul National University College of MedicineSeoulSouth Korea

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