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

Homa Salami,Seyed Javad Mowal,Seyed Abdolhakim Hosseini,Houri Edalat,Rasoul Moukhah,Zahra Hajebrahimi

doi:10.15171/apb.2019.059

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.

Highlights

Some small molecules are capable of alteration of many essential cellular processes such as apoptosis, proliferation and differentiation
A 2 mM valproic acid (VPA) treatment in neural differentiation medium significantly diminished the expression of pluripotency markers and the viability of Wharton’s Jelly mesenchymal stem cells (WJMSCs)
For the first time we propose that VPA has a tolerating effect on the cells to lead them towards homeostasis

Summary

Introduction

Some small molecules are capable of alteration of many essential cellular processes such as apoptosis, proliferation and differentiation. Unlike totipotent (such as dividing egg before blastocyst stage of human development) and pluripotent (such as embryonic stem cells from inner cell mass) stem cells,[8] mesenchymal stem cells (MSCs) are considered as multipotent stem cells that possess many excellent advantages over other kinds of multipotent stem cells They can be readily obtained for autologous grafts with no ethical or rejection problems and are able to differentiate into all three embryonic lineages of ectoderm, endoderm and mesoderm.[9] MSCs can be extracted from adult (such as bone marrow) and even fetal (such as umbilical cord blood and Wharton’s jelly) tissues. Fetal MSCs have less immunerejection problem relative to the adult MSCs.[10] we employed WJMSCs as these cells are acquired and propagated non-aggressively with no ethical or rejection problems To our knowledge, this is the first study on the effects of VPA on potency state and differentiation level of WJMSCs

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