Augmented migration of mesenchymal stem cells correlates with the subsidiary CXCR4 variant

Cell Adh Migr. 2018 Mar 4;12(2):118-126. doi: 10.1080/19336918.2016.1243643. Epub 2018 Feb 27.

Abstract

Use of mesenchymal stem cells (MSCs) has been introduced as a promising tool, for structural and functional recovery of damaged tissues/organs. Studies have indicated that interactions between chemokine receptors and their ligands have a critical role in homing of MSCs to the site of injury. Although CXCR4 variants have been characterized, the exact role of each transcript in homing has remained unclear. In this study, cells were pretreated with various hypoxia-mimicking compounds (valproic acid, cobalt-chloride, and deferoxamine mesylate). Results indicated that both variants of CXCR4 were overexpressed after 24 hours of treatments and their expression could cooperatively induce and promote the cell migration. Moreover, deferoxamine mesylate was more effective in overexpression of variant A (lo), which resulted in higher level of CXCR4 protein and the highest rate of migration of the cells. In conclusion, our findings may have important potential implications in clinical applications, reinforcing the concept that manipulating the expression of specific CXCR4 variants may increase migration of MSCs.

Keywords: CXCR4 variants; SDF1; cobalt-chloride (CoCl2); deferoxamine mesylate (DFX); mesenchymal stem cells' homing; valproic acid (VPA).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Movement / drug effects
  • Deferoxamine / pharmacology
  • Female
  • Humans
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / metabolism*
  • Receptors, CXCR4 / metabolism*
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Valproic Acid / pharmacology

Substances

  • CXCR4 protein, human
  • Receptors, CXCR4
  • Valproic Acid
  • Deferoxamine

Grants and funding

This work was financially supported by Iranian Council of Stem cell Technology (ICST); Academic Center for Education, Culture and Research (ACECR) and Ferdowsi University of Mashhad (FUM).