Targeted Delivery of Bone Marrow Mononuclear Cells by Ultrasound Destruction of Microbubbles Induces Both Angiogenesis and Arteriogenesis Response

Authors:
  • TTTetsuya Tatsumi
    Tetsuya Tatsumi
  • YMYasukiyo Mori
    Yasukiyo Mori
  • TNTakashi Nishiue
    Takashi Nishiue
  • MYMasayuki Yoshida
    Masayuki Yoshida
  • HMHiroya Masaki
    Hiroya Masaki
  • MOMitsuhiko Okigaki
    Mitsuhiko Okigaki
  • HKHiroyuki Kojima
    Hiroyuki Kojima
  • YNYoshihisa Nozawa
    Yoshihisa Nozawa
  • YNYasunobu Nishiwaki
    Yasunobu Nishiwaki
  • NNNoriko Nitta
    Noriko Nitta
  • TIToshiji Iwasaka
    Toshiji Iwasaka
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Abstract
Objective— Ultrasound (US)-mediated destruction of contrast microbubbles causes capillary rupturing that stimulates arteriogenesis, whereas intramuscular implantation (im) of bone marrow mononuclear cells (BM-MNCs) induces angiogenesis. We therefore studied whether US-targeted microbubble destruction combined with transplantation of BM-MNCs can enhance blood flow restoration by stimulating both angiogenesis and arteriogenesis. Methods and Results— US-mediated destruction of phospholipid-coated microbubbles was applied onto ischemic hindlimb muscle and subsequently BM-MNCs were transfused. A significant enhancement in blood flow recovery after Bubble+US+BM-MNC infusion (34% increase, P P Conclusions— This study demonstrates that the targeted delivery of BM-MNCs by US destruction of microbubbles enhances regional angiogenesis and arteriogenesis response, in which the release of platelet-derived proinflammatory factors activated by Bubble+US play a key role in the attachment of transplanted BM-MNCs onto the endothelial layer.

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