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Microbubble destruction with ultrasound augments neovascularisation by bone marrow cell transplantation in rat hind limb ischaemia
  1. S Enomoto1,
  2. M Yoshiyama1,
  3. T Omura1,
  4. R Matsumoto1,
  5. T Kusuyama1,
  6. D Nishiya1,
  7. Y Izumi2,
  8. K Akioka1,
  9. H Iwao2,
  10. K Takeuchi1,
  11. J Yoshikawa1
  1. 1Department of Internal Medicine and Cardiology, Osaka City University Medical School, Osaka, Japan
  2. 2Department of Pharmacology, Osaka City University Medical School, Osaka, Japan
  1. Correspondence to:
    Dr Takashi Omura
    Department of Internal Medicine and Cardiology, Osaka City University Medical School, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan; omura{at}med.osaka-cu.ac.jp

Abstract

Objective: To examine the effects of microbubble destruction with ultrasound (MB) combined with bone marrow derived mononuclear cell transplantation (BMT) into ischaemic tissues in rat hind limb ischaemia.

Methods and results: Unilateral hind limb ischaemia was surgically induced in Lewis rats. At postoperative day 7, rats were randomly divided into three groups: a vehicle treated group, an ultrasound treated group, and an MB treated group. MB treatment increased vascular endothelial growth factor mRNA as assessed by real time polymerase chain reaction (3.0-fold, p < 0.05). At four weeks, the MB group had increases in laser Doppler blood flow index (LDBFI; 1.2-fold, p < 0.05), angiographically detectable collateral vessels (angiographic score: 1.4-fold, p < 0.01), and capillary to muscle fibre ratio (1.4-fold, p < 0.01) in ischaemic limbs compared with the vehicle treated group. No differences were seen between the vehicle and ultrasound treated groups. Secondly, rats were allocated to vehicle treatment, BMT (5 × 106 cells/rat), or a combination of MB and BMT (MB+BMT) at seven days after hind limb ischaemia. BMT treatment significantly increased LDBFI, angiographic score, and capillary to muscle fibre ratio compared with vehicle treatment. Interestingly, MB+BMT treatment produced significantly greater LDBFI (1.2-fold, p < 0.01), angiographic score (1.5-fold, p < 0.01), and capillary to muscle fibre ratio (1.5-fold, p < 0.05) than BMT treatment alone.

Conclusions: MB may be a useful technique to enhance BMT induced neovascularisation.

  • BM-MNC, bone marrow mononuclear cells
  • BMT, bone marrow derived mononuclear cell transplantation
  • EPC, endothelial progenitor cell
  • LDBF, laser Doppler blood flow
  • LDBFI, laser Doppler blood flow index
  • MB, microbubble destruction with ultrasound
  • PCR, polymerase chain reaction
  • VEGF, vascular endothelial growth factor
  • microbubble
  • ultrasound
  • bone marrow mononuclear cells
  • neovascularisation
  • limb ischaemia

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Footnotes

  • Published Online First 1 July 2005

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