Open Access

Valproic acid enforces the priming effect of sphingosine-1 phosphate on human mesenchymal stem cells

  • Authors:
    • Jisun Lim
    • Seungun Lee
    • Hyein Ju
    • Yonghwan Kim
    • Jinbeom Heo
    • Hye-Yeon Lee
    • Kyung-Chul Choi
    • Jaekyoung Son
    • Yeon-Mok Oh
    • In-Gyu Kim
    • Dong-Myung Shin
  • View Affiliations

  • Published online on: July 3, 2017     https://doi.org/10.3892/ijmm.2017.3053
  • Pages: 739-747
  • Copyright: © Lim et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Engraftment and homing of mesenchymal stem cells (MSCs) are modulated by priming factors including the bioactive lipid sphingosine-1-phosphate (S1P), by stimulating CXCR4 receptor signaling cascades. However, limited in vivo efficacy and the remaining priming molecules prior to administration of MSCs can provoke concerns regarding the efficiency and safety of MSC priming. Here, we showed that valproic acid (VPA), a histone deacetylase inhibitor, enforced the priming effect of S1P at a low dosage for human umbilical cord-derived MSCs (UC-MSCs). A DNA-methylation inhibitor, 5-azacytidine (5-Aza), and VPA increased the expression of CXCR4 in UC-MSCs. In particular, UC-MSCs primed with a suboptimal dose (50 nM) of S1P in combination with 0.5 mM VPA (VPA+S1P priming), but not 1 µM 5-Aza, significantly improved the migration activity in response to stromal cell-derived factor 1 (SDF-1) concomitant with the activation of both MAPKp42/44 and AKT signaling cascades. Both epigenetic regulatory compounds had little influence on cell surface marker phenotypes and the multi-potency of UC-MSCs. In contrast, VPA+S1P priming of UC-MSCs potentiated the proliferation, colony forming unit-fibroblast, and anti-inflammatory activities, which were severely inhibited in the case of 5-Aza treatment. Accordingly, the VPA+S1P-primed UC-MSCs exhibited upregulation of a subset of genes related to stem cell migration and anti-inflammation response. Thus, the present study demonstrated that VPA enables MSC priming with S1P at a low dosage by enhancing their migration and other therapeutic beneficial activities. This priming strategy for MSCs may provide a more efficient and safe application of MSCs for treating a variety of intractable disorders.
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September-2017
Volume 40 Issue 3

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Lim J, Lee S, Ju H, Kim Y, Heo J, Lee H, Choi K, Son J, Oh Y, Kim I, Kim I, et al: Valproic acid enforces the priming effect of sphingosine-1 phosphate on human mesenchymal stem cells. Int J Mol Med 40: 739-747, 2017
APA
Lim, J., Lee, S., Ju, H., Kim, Y., Heo, J., Lee, H. ... Shin, D. (2017). Valproic acid enforces the priming effect of sphingosine-1 phosphate on human mesenchymal stem cells. International Journal of Molecular Medicine, 40, 739-747. https://doi.org/10.3892/ijmm.2017.3053
MLA
Lim, J., Lee, S., Ju, H., Kim, Y., Heo, J., Lee, H., Choi, K., Son, J., Oh, Y., Kim, I., Shin, D."Valproic acid enforces the priming effect of sphingosine-1 phosphate on human mesenchymal stem cells". International Journal of Molecular Medicine 40.3 (2017): 739-747.
Chicago
Lim, J., Lee, S., Ju, H., Kim, Y., Heo, J., Lee, H., Choi, K., Son, J., Oh, Y., Kim, I., Shin, D."Valproic acid enforces the priming effect of sphingosine-1 phosphate on human mesenchymal stem cells". International Journal of Molecular Medicine 40, no. 3 (2017): 739-747. https://doi.org/10.3892/ijmm.2017.3053