Hypoxic preconditioning increases survival and angiogenic potency of peripheral blood mononuclear cells via oxidative stress resistance

Masayuki Kubo, Tao Sheng Li, Ryo Suzuki, Bungo Shirasawa, Noriyasu Morikage, Mako Ohshima, Shu Lan Qin, Kimikazu Hamano

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Cell-based angiogenesis is a promising treatment for ischemic diseases; however, the survival of implanted cells is impaired by oxidative stress in the ischemic microenvironment. We tested the hypothesis that hypoxic preconditioning of implanted cells enhances their resistance against oxidative stress, increasing cell survival and angiogenic potency after implantation into ischemic tissue. Mouse peripheral blood mononuclear cells (PBMNCs) were collected and subjected to hypoxic preconditioning by culture for 24 h in 2% O2 at 33°C. Hypoxic preconditioning of PBMNCs increased the expression of various genes related to antioxidant and survival signals remarkably. Compared with cells cultured under normoxia, the hypoxia-preconditioned PBMNCs showed significantly lower reactive oxygen species (ROS) accumulation and higher cell survival under oxidative stress induced by LY-83583 (a superoxide generator). Three days after intramuscular implantation into the ischemic hindlimbs of mice, survival of the hypoxia-preconditioned PBMNCs was high, whereas that of the normoxia-cultured PBMNCs was relatively low. Furthermore, 28 days after treatment microvessel density and blood flow in the ischemic hindlimbs were significantly better in the mice implanted with hypoxia-preconditioned PBMNCs than in those implanted with normoxia-cultured PBMNCs. Hypoxic preconditioning increased the survival and angiogenic potency of PBMNCs, through oxidative stress resistance mechanisms.

Original languageEnglish
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume294
Issue number2
DOIs
Publication statusPublished - Feb 2008
Externally publishedYes

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Blood Cells
Oxidative Stress
Cell Survival
Hindlimb
6-anilino-5,8-quinolinedione
Microvessels
Superoxides
Cultured Cells
Reactive Oxygen Species
Antioxidants
Gene Expression
Hypoxia

Keywords

  • Blood flow
  • Cell therapy
  • Ischemia

ASJC Scopus subject areas

  • Physiology

Cite this

Hypoxic preconditioning increases survival and angiogenic potency of peripheral blood mononuclear cells via oxidative stress resistance. / Kubo, Masayuki; Li, Tao Sheng; Suzuki, Ryo; Shirasawa, Bungo; Morikage, Noriyasu; Ohshima, Mako; Qin, Shu Lan; Hamano, Kimikazu.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 294, No. 2, 02.2008.

Research output: Contribution to journalArticle

Kubo, Masayuki ; Li, Tao Sheng ; Suzuki, Ryo ; Shirasawa, Bungo ; Morikage, Noriyasu ; Ohshima, Mako ; Qin, Shu Lan ; Hamano, Kimikazu. / Hypoxic preconditioning increases survival and angiogenic potency of peripheral blood mononuclear cells via oxidative stress resistance. In: American Journal of Physiology - Heart and Circulatory Physiology. 2008 ; Vol. 294, No. 2.
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