Implantation of Adipose-Derived Regenerative Cells Enhances Ischemia-Induced Angiogenesis

  • Kazuhisa Kondo
    From the Department of Cardiology (K.K., S.S., R.S., H.M., R.M., T.M.), Nagoya University Graduate School of Medicine, and the Department of Bioengineering Sciences (M.I., Y.K.), Nagoya University Graduated School of Bioagricultural Sciences, Nagoya, Japan.
  • Satoshi Shintani
    From the Department of Cardiology (K.K., S.S., R.S., H.M., R.M., T.M.), Nagoya University Graduate School of Medicine, and the Department of Bioengineering Sciences (M.I., Y.K.), Nagoya University Graduated School of Bioagricultural Sciences, Nagoya, Japan.
  • Rei Shibata
    From the Department of Cardiology (K.K., S.S., R.S., H.M., R.M., T.M.), Nagoya University Graduate School of Medicine, and the Department of Bioengineering Sciences (M.I., Y.K.), Nagoya University Graduated School of Bioagricultural Sciences, Nagoya, Japan.
  • Hisashi Murakami
    From the Department of Cardiology (K.K., S.S., R.S., H.M., R.M., T.M.), Nagoya University Graduate School of Medicine, and the Department of Bioengineering Sciences (M.I., Y.K.), Nagoya University Graduated School of Bioagricultural Sciences, Nagoya, Japan.
  • Ryuichiro Murakami
    From the Department of Cardiology (K.K., S.S., R.S., H.M., R.M., T.M.), Nagoya University Graduate School of Medicine, and the Department of Bioengineering Sciences (M.I., Y.K.), Nagoya University Graduated School of Bioagricultural Sciences, Nagoya, Japan.
  • Masayasu Imaizumi
    From the Department of Cardiology (K.K., S.S., R.S., H.M., R.M., T.M.), Nagoya University Graduate School of Medicine, and the Department of Bioengineering Sciences (M.I., Y.K.), Nagoya University Graduated School of Bioagricultural Sciences, Nagoya, Japan.
  • Yasuo Kitagawa
    From the Department of Cardiology (K.K., S.S., R.S., H.M., R.M., T.M.), Nagoya University Graduate School of Medicine, and the Department of Bioengineering Sciences (M.I., Y.K.), Nagoya University Graduated School of Bioagricultural Sciences, Nagoya, Japan.
  • Toyoaki Murohara
    From the Department of Cardiology (K.K., S.S., R.S., H.M., R.M., T.M.), Nagoya University Graduate School of Medicine, and the Department of Bioengineering Sciences (M.I., Y.K.), Nagoya University Graduated School of Bioagricultural Sciences, Nagoya, Japan.

抄録

<jats:p> <jats:bold> <jats:italic>Objective—</jats:italic> </jats:bold> Therapeutic angiogenesis using autologous stem/progenitor cells represents a novel strategy for severe ischemic diseases. Recent reports indicated that adipose tissues could supply adipose-derived regenerative cells (ADRCs). Accordingly, we examined whether implantation of ADRCs would augment ischemia-induced angiogenesis. </jats:p> <jats:p> <jats:bold> <jats:italic>Method and Results—</jats:italic> </jats:bold> Adipose tissue was obtained from C57BL/6J mice, and ADRCs were isolated using standard methods. ADRCs expressed stromal cell–derived factor 1 (SDF-1) mRNA and proteins. Hind limb ischemia was induced and culture-expanded ADRCs, PBS, or mature adipocytes (MAs) as control cells were injected into the ischemic muscles. At 3 weeks, the ADRC group had a greater laser Doppler blood perfusion index and a higher capillary density compared to the controls. Implantation of ADRCs increased circulating endothelial progenitor cells (EPCs). SDF-1 mRNA abundance at ischemic tissues and serum SDF-1 levels were greater in the ADRC group than in the control group. Finally, intraperitoneal injection of an anti–SDF-1 neutralizing antibody reduced the number of circulating EPCs and therapeutic efficacies of ADRCs. </jats:p> <jats:p> <jats:bold> <jats:italic>Conclusions—</jats:italic> </jats:bold> Adipose tissue would be a valuable source for cell-based therapeutic angiogenesis. Moreover, chemokine SDF-1 may play a pivotal role in the ADRCs-mediated angiogenesis at least in part by facilitating mobilization of EPCs. </jats:p>

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