Cellular and Molecular Neurobiology

, Volume 36, Issue 4, pp 613–620 | Cite as

Functional Restoration of Amyotrophic Lateral Sclerosis Patient-Derived Mesenchymal Stromal Cells Through Inhibition of DNA Methyltransferase

  • Youn Seo Oh
  • Seung Hyun Kim
  • Goang-Won ChoEmail author
Original Research


Alteration of DNA methylation is highly associated with aging and neurodegenerative disorders, such as amyotrophic lateral sclerosis (ALS). Remedying these aberrant methylation patterns may serve to improve these diseases. Previously, we reported that human bone marrow mesenchymal stromal cells isolated from ALS patients (ALS-MSCs) have functionally decreased stem cell potency, and excessively express DNA methyltransferases (DNMTs). In this study, we examined the correlation between excessive DNMT expression and functional decline in ALS-MSCs. The DNMT inhibitor RG108 was used for this. RG108-treated ALS-MSCs exhibit increased expression of the anti-senescence genes TERT, VEGF, and ANG, and decreased expression of the senescence-related genes ATM and p21. The activity of SA-β-galactosidase and the expression of senescence proteins p53 and p16 were reduced in RG108-treated ALS-MSCs. The abilities of cell migration and protection against oxidative damage were improved in the treated ALS-MSCs. In neuronal differentiation experiments, the treated MSCs more effectively differentiated into neuron-like cells. These results suggest that ALS-MSC function can be restored by inhibiting excessively expressed DNMTs, an approach that may ultimately provide better efficacy in stem cell therapy.


Bone marrow mesenchymal stromal cells (BM-MSCs) Amyotrophic lateral sclerosis (ALS) DNA methyltransferases (DNMTs) DNMT inhibition RG108 



Amyotrophic lateral sclerosis




Ataxia telangiectasia mutated


Butyalated hydroxyanisole


Bone marrow mesenchymal stromal cells


Dimethyl sulfoxide


DNA methyltransferases


Fetal bovine serum




Mesenchymal stromal cells


3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide


Phosphate-buffered saline


Polymerase chain reaction


Radioimmunoprecipitation assay

SA-β-gal staining

Senescence-associated beta-galactosidase staining




Vascular endothelial growth factor



This work was supported by a grant from the Korea Healthcare Technology R&D Project, Ministry for Health, Welfare & Family Affairs, Republic of Korea (A120203), a grant from the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (NRF-2010-0010431).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflicts of interest.

Ethical standards

The manuscript does not contain clinical studies or patient data.

Supplementary material

10571_2015_242_MOESM1_ESM.docx (14 kb)
Supplementary material 1 (DOCX 14 kb)


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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Youn Seo Oh
    • 1
    • 2
  • Seung Hyun Kim
    • 3
    • 4
  • Goang-Won Cho
    • 1
    • 2
    Email author
  1. 1.Department of Biology, College of Natural ScienceChosun UniversityGwangjuKorea
  2. 2.Department of Life Science, BK21-Plus Research Team for Bioactive Control TechnologyChosun UniversityGwangjuKorea
  3. 3.Department of NeurologyHanyang University College of MedicineSeoulKorea
  4. 4.Cell Therapy CenterHanyang University HospitalSeoulKorea

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