Ex vivo activation of angiogenic property in human peripheral blood-derived monocytes by thrombopoietin.

Abstract

Human peripheral blood mononuclear cells (PB-MNCs) have angiogenic properties, which make them promising cells for use in angiogenic therapy approaches in regenerative medicine. To explore an efficient method for expanding pro-angiogenic cells from PB-MNCs, we developed a novel serum-free culture system composed of X-VIVO15 medium supplemented with vascular endothelial growth factor, basic fibroblast growth factor, and thrombopoietin (TPO). Using this ex vivo culture, we obtained floating spheres composed mainly of CD11b(+) monocytes expressing c-Mpl (TPO receptor) and which exhibited acetylated low-density lipoprotein uptake and phagocytosis. Expression of IL-8, CXCR4, and vasohibin-2 mRNA was upregulated in these cells. In the presence of TPO, the number and size of the spheres were increased. In a nude mouse hind-limb ischemia model, the intramuscular injection of spheroid cells treated with TPO rescued blood perfusion more effectively than that without TPO. These results indicate that the ex vivo addition of TPO augments the pro-angiogenic activity of peripheral CD11b(+) monocytes, suggesting that this method shows promise for uses in human cell therapy aimed at the induction of vascular regeneration by activating the angiogenic properties of human peripheral blood-derived monocytes.

• Authors: Toru Kawamoto, Junpei Sasajima, Yoshiaki Sugiyama, Kazumasa Nakamura, Hiroki Tanabe, Mikihiro Fujiya, Toshie Nata, Yasuyuki Iuchi, Toshifumi Ashida, Yoshihiro Torimoto, Yusuke Mizukami, Yutaka Kohgo
• Journal: International journal of hematology (Int J Hematol) Vol. 98 Issue 4 Pg. 417-29 (Oct 2013) ISSN: 1865-3774 [Electronic] Japan
• PMID: 24002641 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CD11b Antigen
• Culture Media, Serum-Free
• Thrombopoietin

Topics

• Animals
• CD11b Antigen (metabolism)
• Cell Culture Techniques
• Culture Media, Serum-Free
• Female
• Hindlimb (blood supply, metabolism)
• Humans
• Ischemia (metabolism)
• Leukocytes, Mononuclear (drug effects, metabolism)
• Mice
• Monocytes (drug effects, metabolism)
• Neovascularization, Physiologic (drug effects)
• Phenotype
• Thrombopoietin (pharmacology)