Benefit of combined extracorporeal shock wave and bone marrow-derived endothelial progenitor cells in protection against critical limb ischemia in rats

Kuo Ho Yeh*, Jiunn Jye Sheu, Yu Chun Lin, Cheuk Kwan Sun, Li Teh Chang, Ying Hsien Kao, Chia Hong Yen, Pei Lin Shao, Tzu Hsien Tsai, Yung Lung Chen, Sarah Chua, Steve Leu, Hon Kan Yip

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

58 Scopus citations

Abstract

Objectives: We hypothesized that combined treatment with extracorporeal shock wave and bone marrow-derived endothelial progenitor cells might exert enhanced protection against critical limb ischemia in rats. Methods: Male Sprague-Dawley rats (n = 9 for laser Doppler study and n = 6 for laboratory examinations in each group) were divided into group 1 (sham control), group 2 (critical limb ischemia treated with culture medium), group 3 (critical limb ischemia treated with intramuscular bone marrow-derived endothelial progenitor cells [2.0 × 10 cells]), group 4 (critical limb ischemia treated with extracorporeal shock wave [280 impulses at 0.1 mJ/mm]), and group 5 (combined bone marrow-derived endothelial progenitor cell-extracorporeal shock wave) after critical limb ischemia induction. Results: By day 21, laser Doppler showed substantially lower ratios of ischemic/normal blood flow in group 2 compared with other groups (p < .001). The protein expressions of mitochondrial cytochrome c, stromal cell-derived factor-1, C-X-C chemokine receptor type 4, vascular endothelial growth factor, and endothelial nitric oxide synthase were remarkably higher in group 5 than in groups 2 to 4, and notably higher in groups 3 and 4 than in group 2 (all p < .01). The messenger RNA expressions of proinflammatory and apoptotic biomarkers and oxidative stress were reduced in group 5 compared with groups 2 to 4, and notably lower in groups 3 and 4 than in group 2 (all p < .01). The messenger RNA expressions of anti-inflammatory and antiapoptotic biomarkers were lower in group 2 than in other groups (all p < .01). Immunofluorescent staining showed higher numbers of CD31+ stromal cell-derived factor-1+, chemokine receptor type 4+, and von Willebrand factor+ cells, and vessels in the ischemic area in group 5 than in groups 2 to 4, and in groups 3 and 4 than in group 2 (all p < .04). Conclusion: Combined treatment with bone marrow-derived endothelial progenitor cells and extracorporeal shock wave is superior to either bone marrow-derived endothelial progenitor cells or extracorporeal shock wave alone in improving ischemia in rodent critical limb ischemia.

Original languageEnglish
Pages (from-to)169-177
Number of pages9
JournalCritical Care Medicine
Volume40
Issue number1
DOIs
StatePublished - 01 2012

Keywords

  • Angiogenesis
  • Critical limb ischemia
  • Endothelial progenitor cells
  • Extracorporeal shock wave

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