Drug Res (Stuttg) 2018; 68(08): 450-456
DOI: 10.1055/s-0044-102007
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Histone Deacetylase Inhibitor (Trapoxin A) Enhances Stemness Properties in Adipose Tissue Derived Mesenchymal Stem Cells

Leila Mousazadeh
1   The Umbilical Cord Stem Cell Research Center (UCSRC), Tabriz University of Medical Sciences, Tabriz, Iran
2   Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
,
Effat Alizadeh
1   The Umbilical Cord Stem Cell Research Center (UCSRC), Tabriz University of Medical Sciences, Tabriz, Iran
2   Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
,
Nosratollah Zarghami
1   The Umbilical Cord Stem Cell Research Center (UCSRC), Tabriz University of Medical Sciences, Tabriz, Iran
2   Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
,
Shahryar Hashemzadeh
3   Department of General Surgery, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
,
Sedigheh Fekri Aval
2   Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
,
Leili Hasanifard
4   Department of Clinical Biochemistry, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
,
Roya Herizchi
2   Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
› Author Affiliations
Further Information

Publication History

received 17 November 2017

accepted 29 January 2018

Publication Date:
26 February 2018 (online)

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Abstract

Back ground Adipose tissue derived mesenchymal stem cells (ASCs) have unique potential for regenerative cell therapies. However, during ex-vivo cultivation, they undergo considerable quality loss regarding their phenotypic properties, stemness genes expression and differentiation potential. Recent studies reported that the loss of stemness properties of MSCs is a result of chromatin histone deacetylations through in-vitro cultivation. The present work aimed to study the effect of Trapoxin A (TPX) as a histone deacetylase inhibitor (HDACi) on overall stemness properties of ASCs.

Methods First, the effects of TPX treatments on ASCs viability and proliferation were evaluated using MTT assay. Second, the desired doses of TPX supporting ASCs proliferation were determined and the lack of their negative effects was confirmed by DAPI staining. In addition, the influence of TPX on cell cycle of ASCs and the mRNA levels of stemness genes were measured by flowcytometry and qPCR, respectively. Finally, the effect of TPX treatment on osteogenic potential of ASCs was studied.

Results The results indicated that short time TPX treatment (nM concentrations) caused stimulation of proliferation and considerable percentage of ASCs entered to S-phase of cell cycle (p<0.05). Moreover, the findings demonstrated significant up-regulation of stemness markers genes (Oct-4, Sox-2, Nanog, TERT, Klf-4, Rex-1) (p<0.05) and enhanced osteogenic differentiation potential of ASC after TPX treatment.

Conclusion The addition of low dose of TPX to the expansion medium could possibly enhance the stemness properties and prevent the quality decline of ex-vivo cultured ASCs.