International Journal of Hematology

, Volume 98, Issue 4, pp 417–429 | Cite as

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

  • Toru Kawamoto
  • Junpei Sasajima
  • Yoshiaki Sugiyama
  • Kazumasa Nakamura
  • Hiroki Tanabe
  • Mikihiro Fujiya
  • Toshie Nata
  • Yasuyuki Iuchi
  • Toshifumi Ashida
  • Yoshihiro Torimoto
  • Yusuke Mizukami
  • Yutaka Kohgo
Original Article
First Online:
Received:
Revised:
Accepted:

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.

Keywords

Thrombopoietin Ex vivo culture CD11b+ monocytes Spheroid Angiogenesis 
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Notes

Acknowledgements

This study was supported by research funding to Y.M. from the New Energy and Industrial Technology Development Organization of Japan (07A05010a) and a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, Sports, and Culture of Japan (22590754).

Conflict of interest

The authors declare no competing financial interests.

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Copyright information

© The Japanese Society of Hematology 2013

Authors and Affiliations

  • Toru Kawamoto
    • 1
  • Junpei Sasajima
    • 1
  • Yoshiaki Sugiyama
    • 1
  • Kazumasa Nakamura
    • 1
  • Hiroki Tanabe
    • 1
  • Mikihiro Fujiya
    • 1
  • Toshie Nata
    • 3
  • Yasuyuki Iuchi
    • 3
  • Toshifumi Ashida
    • 1
    • 3
  • Yoshihiro Torimoto
    • 1
    • 4
  • Yusuke Mizukami
    • 1
    • 2
    • 3
  • Yutaka Kohgo
    • 1
  1. 1.Division of Gastroenterology and Hematology/Oncology, Department of MedicineAsahikawa Medical UniversityAsahikawaJapan
  2. 2.Gastrointestinal UnitMassachusetts General Hospital and Harvard Medical SchoolBostonUSA
  3. 3.Clinical Research CenterSapporo Higashi Tokusyukai HospitalSapporoJapan
  4. 4.Oncology CenterAsahikawa Medical University HospitalAsahikawaJapan

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