Increased expression of CXCR4 and integrin αM in hypoxia- preconditioned cells contributes to improved cell retention and angiogenic potency

Masayuki Kubo, Tao Sheng Li, Takahiro Kamota, Mako Ohshima, Shu Lan Qin, Kimikazu Hamano

Research output: Contribution to journalArticle

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Abstract

Cell-based angiogenesis is a promising method for the treatment of ischemic diseases, but the poor retention of implanted cells in targeted tissues is a major drawback.Wetested whether hypoxic preconditioning increased retention and angiogenic potency of implanted cells in ischemic tissue. Hypoxic preconditioning of mouse peripheral blood mononuclear cells (PBMNCs) was done with 24 h of culture under 2% O2. Normoxia-cultured PBMNCs were used as a control. Hypoxic preconditioning increased the adhesion capacity of the PBMNCs. Moreover, the expression of integrin aM and CXCR4 was significantly higher in the hypoxia-preconditioned PBMNCs than in the normoxia-cultured PBMNCs. Interestingly, the expression of intercellular adhesion molecule-1 (ICAM-1), a ligand of integrin aM, and stromal cell-derived factor-1 (SDF-1), a chemokine for CXCR4, were remarkably increased in the ischemic hindlimbs. The retention of the hypoxia-preconditioned PBMNCs was significantly higher than that of the normoxia-cultured PBMNCs, 3 days after their intramuscular implantation into ischemic hindlimbs. We also noted better blood flow in the ischemic hindlimbs implanted with the hypoxiapreconditioned PBMNCs than in those implanted with the normoxia-cultured PBMNCs, 14 days after treatment. Furthermore, antibody neutralization of integrin αM and CXCR4 abolished completely the increased cell retention and angiogenic potency of the hypoxia-preconditioned PBMNCs after implantation into the ischemic hindlimbs. These results indicate that hypoxic preconditioning of implanted cells is a feasible method of enhancing therapeutic angiogenesis by increasing their retention.

Original languageEnglish
Pages (from-to)508-514
Number of pages7
JournalJournal of Cellular Physiology
Volume220
Issue number2
DOIs
Publication statusPublished - Aug 2009
Externally publishedYes

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Cell Hypoxia
Integrins
Blood Cells
Blood
Hindlimb
Chemokine CXCL12
Tissue
Intercellular Adhesion Molecule-1
Chemokines
Cell culture
Adhesion
Ligands

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

Increased expression of CXCR4 and integrin αM in hypoxia- preconditioned cells contributes to improved cell retention and angiogenic potency. / Kubo, Masayuki; Li, Tao Sheng; Kamota, Takahiro; Ohshima, Mako; Qin, Shu Lan; Hamano, Kimikazu.

In: Journal of Cellular Physiology, Vol. 220, No. 2, 08.2009, p. 508-514.

Research output: Contribution to journalArticle

Kubo, Masayuki ; Li, Tao Sheng ; Kamota, Takahiro ; Ohshima, Mako ; Qin, Shu Lan ; Hamano, Kimikazu. / Increased expression of CXCR4 and integrin αM in hypoxia- preconditioned cells contributes to improved cell retention and angiogenic potency. In: Journal of Cellular Physiology. 2009 ; Vol. 220, No. 2. pp. 508-514.
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