Hypoxically preconditioned human peripheral blood mononuclear cells improve blood flow in hindlimb ischemia xenograft model

Tomoaki Kudo, Masayuki Kubo, Shunsaku Katsura, Arata Nishimoto, Koji Ueno, Makoto Samura, Yasuhiko Fujii, Tohru Hosoyama, Kimikazu Hamano

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Transplantation of peripheral blood mononuclear cells (PBMNCs) is a promising therapeutic approach for the treatment of hindlimb ischemia. However, insufficient angiogenesis in ischemic hindlimb after cell transplantation reduces the importance and practicality of this approach. Previously, we demonstrated using mouse models that hypoxic preconditioning augmented the cellular functions of rodent PBMNCs, such as increased cell adhesion capacity and accelerated neovascularization in ischemic hindlimb. To test the clinical application of this therapeutic strategy in this study, we investigated whether the protocol of hypoxic preconditioning, which was established in a condition of 2% O2 for 24 h, can be made available for human PBMNCs (hPBMNCs). In addition, we grafted preconditioned hPBMNCs in a hindlimb ischemia mouse model. Hypoxic preconditioning enhanced cell adhesion capacity and oxidative stress resistance in hPBMNCs. We also observed an up-regulation of platelet endothelial cell adhesion molecule-1 (PECAM-1) in hPBMNCs by hypoxic preconditioning. Furthermore, preconditioned hPBMNCs significantly recovered limb blood flow in ischemic mice after transplantation. These results indicate that our established preconditioning protocol is available for hPBMNCs to effectively reinforce multiple cellular functions. Taken together with our series of study, we believe that this simple but powerful therapeutic strategy will be helpful in curing patients with severe hindlimb ischemia.

Original languageEnglish
Pages (from-to)570-579
Number of pages10
JournalAmerican Journal of Translational Research
Volume6
Issue number5
Publication statusPublished - 2014

Keywords

  • Cell-Based therapy
  • Hindlimb ischemia
  • Human peripheral blood mononuclear cells
  • Hypoxic preconditioning
  • Therapeutic angiogenesis

ASJC Scopus subject areas

  • Molecular Medicine
  • Clinical Biochemistry
  • Cancer Research

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    Kudo, T., Kubo, M., Katsura, S., Nishimoto, A., Ueno, K., Samura, M., Fujii, Y., Hosoyama, T., & Hamano, K. (2014). Hypoxically preconditioned human peripheral blood mononuclear cells improve blood flow in hindlimb ischemia xenograft model. American Journal of Translational Research, 6(5), 570-579.