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Adv Pharm Bull. 2019;9(3): 497-504.
doi: 10.15171/apb.2019.059
PMID: 31592436
PMCID: PMC6773934
Scopus ID: 85070478620
  Abstract View: 360
  PDF Download: 258

Research Article

Evaluating the Differential Effects of Valproic Acid on Wharton’s Jelly Mesenchymal Stem Cells

Homa Salami 1, Seyed Javad Mowal 1 ORCID logo, Rasoul Moukhah 2, Zahra Hajebrahimi 3 ORCID logo, Seyed Abdolhakim Hosseini 4 ORCID logo, Houri Edalat 5 * ORCID logo

1 Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.
2 Quality assurance Department, Production and Research Complex, Pasteur Institute of Iran, Tehran, Iran.
3 Aerospace Research Institute, Ministry of Science, Research and Technology, Tehran, Iran.
4 Molecular Medicine Center, Hamadan University of Medical Sciences, Hamadan, Iran.
5 Human Genetics Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.

Abstract

Purpose: The histone deacetylases (HDAC) inhibitor, valproic acid (VPA), is a common antiepileptic drug and is attractive for its broad range of therapeutic effects on many diseases. It has been employed as an inducer of pluripotency in some cultured cells. Conversely, VPA has also been employed as an inducer of in vitro differentiation in many other cells. Therefore, we employed WJMSCs as a cellular target to evaluate the differential effects of of VPA on potency state and differentiation level of Wharton’s Jelly mesenchymal stem cells (WJMSCs) in various concentrations and different culture mediums.

Methods: The isolated WJMSCs were cultured in DMEM (MSC medium). According to previous protocols, WJMSCs were treated with 0, 0.5 and 1 mM VPA in MSC or embryonic stem cell (ESC) medium and 2 mM VPA in neural differentiation medium. Real-time polymerase chain reaction (PCR) and western blot analysis were performed for evaluating the expression of pluripotency markers. MTT and caspase assays were also performed on VPA-treated cells.

Results: The expression of pluripotency markers and the viability of the WJMSCs – determined by MTT assay – were significantly increased after 0.5 mM VPA treatment in ESC medium. A 2 mM VPA treatment in neural differentiation medium significantly diminished the expression of pluripotency markers and the viability of WJMSCs.

Conclusion: According to our results, both VPA concentration and the medium context can influence VPA effects on WJMSCs. The differential effects of VPA on WJMSCs can reflect its wide range of effects in the treatment of various diseases.

Keywords: Valproic acid, Wharton’s jelly mesenchymal stem cells, Potency, Neural differentiation
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Submitted: 12 Feb 2019
Revision: 31 Mar 2019
Accepted: 14 Apr 2019
ePublished: 01 Aug 2019
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