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

42 Citations (Scopus)

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 1 2009

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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