Combination of In Vivo Angiopoietin-1 Gene Transfer and Autologous Bone Marrow Cell Implantation for Functional Therapeutic Angiogenesis

DOI Web Site 被引用文献7件
  • Koichi Kobayashi
    From the Departments of Cardiology (K. Kobayashi, T.K., N.I., M.A., T. M.), Molecular Neurosurgery (M.M.), Vascular Surgery (K. Komori), and Neurosurgery (M.M., J.Y.), Nagoya University Graduate School of Medicine, Nagoya, Japan
  • Takahisa Kondo
    From the Departments of Cardiology (K. Kobayashi, T.K., N.I., M.A., T. M.), Molecular Neurosurgery (M.M.), Vascular Surgery (K. Komori), and Neurosurgery (M.M., J.Y.), Nagoya University Graduate School of Medicine, Nagoya, Japan
  • Natsuo Inoue
    From the Departments of Cardiology (K. Kobayashi, T.K., N.I., M.A., T. M.), Molecular Neurosurgery (M.M.), Vascular Surgery (K. Komori), and Neurosurgery (M.M., J.Y.), Nagoya University Graduate School of Medicine, Nagoya, Japan
  • Mika Aoki
    From the Departments of Cardiology (K. Kobayashi, T.K., N.I., M.A., T. M.), Molecular Neurosurgery (M.M.), Vascular Surgery (K. Komori), and Neurosurgery (M.M., J.Y.), Nagoya University Graduate School of Medicine, Nagoya, Japan
  • Masaaki Mizuno
    From the Departments of Cardiology (K. Kobayashi, T.K., N.I., M.A., T. M.), Molecular Neurosurgery (M.M.), Vascular Surgery (K. Komori), and Neurosurgery (M.M., J.Y.), Nagoya University Graduate School of Medicine, Nagoya, Japan
  • Kimihiro Komori
    From the Departments of Cardiology (K. Kobayashi, T.K., N.I., M.A., T. M.), Molecular Neurosurgery (M.M.), Vascular Surgery (K. Komori), and Neurosurgery (M.M., J.Y.), Nagoya University Graduate School of Medicine, Nagoya, Japan
  • Jun Yoshida
    From the Departments of Cardiology (K. Kobayashi, T.K., N.I., M.A., T. M.), Molecular Neurosurgery (M.M.), Vascular Surgery (K. Komori), and Neurosurgery (M.M., J.Y.), Nagoya University Graduate School of Medicine, Nagoya, Japan
  • Toyoaki Murohara
    From the Departments of Cardiology (K. Kobayashi, T.K., N.I., M.A., T. M.), Molecular Neurosurgery (M.M.), Vascular Surgery (K. Komori), and Neurosurgery (M.M., J.Y.), Nagoya University Graduate School of Medicine, Nagoya, Japan

抄録

<jats:p> <jats:bold> <jats:italic>Objective—</jats:italic> </jats:bold> Autologous bone marrow mononuclear cell (BM-MNC) implantation into ischemic tissues promotes angiogenesis, but a large amount of marrow aspiration is required, which is a major clinical limitation. Angiopoietin-1 (Ang-1) is requisite for vascular maturation during angiogenesis. We examined the impacts of combinatorial Ang-1 gene transfer and low-dose autologous BM-MNC implantation on therapeutic angiogenesis in a rabbit model of hind limb ischemia. </jats:p> <jats:p> <jats:bold> <jats:italic>Methods and Results—</jats:italic> </jats:bold> Rabbits were divided into 4 groups: phosphate-buffered saline (control), 500 μg Ang-1 plasmid (Ang-1), 1×10 <jats:sup>6</jats:sup> autologous BM-MNCs (BMC), and Ang-1 plasmid plus BM-MNCs (combination). The Ang-1 group had a greater angiographic score and capillary density compared with the control ( <jats:italic>P</jats:italic> <0.05), but the Ang-1 gene therapy alone did not improve transcutaneous oxygen pressure (TcO <jats:sub>2</jats:sub> ) and skin ulcer score. However, the combination group showed a significant improvement in not only angiographic score and capillary density ( <jats:italic>P</jats:italic> <0.05) but also TcO <jats:sub>2</jats:sub> ( <jats:italic>P</jats:italic> <0.05) and skin ulcer score. These efficacies were greater in the combination group compared with the BMC group. </jats:p> <jats:p> <jats:bold> <jats:italic>Conclusions—</jats:italic> </jats:bold> This Ang-1 gene and BM-MNC combination therapy enhances not only quantitative but also qualitative angiogenesis in ischemic tissues. Moreover, the combination therapy will enable a reduction in the amount of BM aspiration required for significant therapeutic angiogenesis. </jats:p>

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