Up-regulation of miR-210 by vascular endothelial growth factor in ex vivo expanded CD34+ cells enhances cell-mediated angiogenesis

Mohamad Amer Alaiti, Masakazu Ishikawa, Haruchika Masuda, Daniel I. Simon, Mukesh K. Jain, Takayuki Asahara, Marco A. Costa

Research output: Contribution to journalArticlepeer-review

65 Scopus citations

Abstract

Ex vivo culture has been proposed as a means to augment and repair autologous cells in patients with chronic diseases, but the mechanisms governing improvement in cell function are not well understood. Although microRNAs (miRs) are increasingly appreciated as key regulators of cellular function, a role for these factors in CD34+ cell-mediated angiogenesis has not been elucidated. Vascular endothelial growth factor (VEGF) was previously shown to induce expression of certain miRs associated with angiogenesis in endothelial cells and promote survival and number of vascular colony forming units of haematopoietic stem cells (HSCs). We sought to evaluate the role of VEGF in expansion and angiogenic function of CD34+ cells and to identify specific miRs associated with angiogenic properties of expanded cells. Umbilical cord blood CD34+ cells were effectively expanded (18- to 22-fold) in culture medium containing stem cell factor (SCF), Flt-3 ligand (Flt-3), thrombopoietin (TPO) and interleukin-6 (IL-6) with (postEX/+VEGF) and without VEGF (postEX/noVEGF). Tube formation in matrigel assay and tissue perfusion/capillary density in mice ischaemic hindlimb were significantly improved by postEX/+VEGF cells compared with fresh CD34+ and postEX/noVEGF cells. MiR-210 expression was significantly up-regulated in postEX/+VEGF cells. MiR-210 inhibitor abrogated and 210 mimic recapitulated the pro-angiogenic effects by treatment of postEX/+VEGF and postEX/noVEGF cells respectively. Collectively, these observations highlight a critical role for VEGF in enhancing the angiogenic property of expanded cells, and identify miR-210 as a potential therapeutic target to enhance CD34+ stem cell function for the treatment of ischaemic vascular disease.

Original languageEnglish (US)
Pages (from-to)2413-2421
Number of pages9
JournalJournal of Cellular and Molecular Medicine
Volume16
Issue number10
DOIs
StatePublished - Oct 2012
Externally publishedYes

Keywords

  • Angiogenesis
  • CD34+ cells
  • MiR-210
  • VEGF

ASJC Scopus subject areas

  • Molecular Medicine
  • Cell Biology

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