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Stem Cells International
Volume 2014 (2014), Article ID 610495, 14 pages
http://dx.doi.org/10.1155/2014/610495
Research Article

Migration, Proliferation, and Differentiation of Cord Blood Mesenchymal Stromal Cells Treated with Histone Deacetylase Inhibitor Valproic Acid

1Centre for Innovation (Formerly Research & Development), Canadian Blood Services, 8249-112 Street, Edmonton, AB, Canada T6G 2R8
2Division of Hematology, Department of Medicine, University of Alberta, 8440-112 Street, Edmonton, AB, Canada T6G 2B7

Received 25 June 2013; Revised 30 January 2014; Accepted 4 February 2014; Published 16 March 2014

Academic Editor: Pavla Jendelova

Copyright © 2014 Leah A. Marquez-Curtis et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Mesenchymal stromal cells (MSC) have great potential for cellular therapies as they can be directed to differentiate into certain lineages or to exert paracrine effects at sites of injury. The interactions between stromal cell-derived factor (SDF)-1 and its receptors CXCR4 and CXCR7 play pivotal roles in the migration of MSC to injured tissues. We evaluated whether a histone deacetylase inhibitor valproic acid (VPA) modulates the migration of cord blood (CB-) derived MSC towards SDF-1 and their proliferation and differentiation. We found that in MSC, VPA increased (i) the gene and total protein expression of CXCR4 and CXCR7 and primed migration towards a low gradient of SDF-1, (ii) the gene expression of MMP-2 and secretion and activation of proMMP-2, (iii) the proliferation and gene expression of pluripotency markers SOX2 and Oct-4, and exposure to lower concentrations of VPA (≤5 mM) had no effect on their differentiation to osteocytes and chondrocytes. Thus, our study indicates that VPA enhances the migration of CB MSC towards SDF-1 by increasing the expression of CXCR4, CXCR7, and MMP-2. VPA at low concentrations may be used for ex vivo treatment of MSC to increase their recruitment to sites of injury without compromising their ability to proliferate or differentiate.