Open AccessUp‐regulation of miR‐210 by vascular endothelial growth factor in ex vivo expanded CD 34+ cells enhances cell‐mediated angiogenesis
Author(s) -
Alaiti Mohamad Amer,
Ishikawa Masakazu,
Masuda Haruchika,
Simon Daniel I.,
Jain Mukesh K.,
Asahara Takayuki,
Costa Marco A.
Publication year - 2012
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2012.01557.x
Subject(s) - ex vivo , angiogenesis , matrigel , microbiology and biotechnology , vascular endothelial growth factor , haematopoiesis , stem cell , vascular endothelial growth factor a , biology , endothelial stem cell , thrombopoietin , cancer research , chemistry , immunology , in vitro , vegf receptors , biochemistry
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 micro RNA s (miRs) are increasingly appreciated as key regulators of cellular function, a role for these factors in CD 34+ 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 ( HSC s). We sought to evaluate the role of VEGF in expansion and angiogenic function of CD 34+ cells and to identify specific miRs associated with angiogenic properties of expanded cells. Umbilical cord blood CD 34+ 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 (post EX /+ VEGF ) and without VEGF (post EX /no VEGF ). Tube formation in matrigel assay and tissue perfusion/capillary density in mice ischaemic hindlimb were significantly improved by post EX /+ VEGF cells compared with fresh CD 34+ and post EX /no VEGF cells. MiR‐210 expression was significantly up‐regulated in post EX /+ VEGF cells. MiR‐210 inhibitor abrogated and 210 mimic recapitulated the pro‐angiogenic effects by treatment of post EX /+ VEGF and post EX /no VEGF 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 CD 34+ stem cell function for the treatment of ischaemic vascular disease.