Title page for etd-0216117-100714


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URN etd-0216117-100714
Author Shih-Ya Tseng
Author's Email Address hero4811@gmail.com
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Department Biological Sciences
Year 2016
Semester 2
Degree Ph.D.
Type of Document
Language English
Title Cilostazol increases proangiogeneic functions of human early endothelial progenitor cells and hybrid therapy provides a synergistic treatment effect to hindlimb ischemia animal model
Date of Defense 2017-02-24
Page Count 91
Keyword
  • Peripheral artery disease
  • Critical limb ischemia
  • Angiogenesis
  • Cilostazol
  • SDF-1α
  • Endothelial progenitor cells
  • Abstract Critical limb ischemia (CLI) is an advanced form of peripheral artery disease in which the narrowing arteries limit blood supply to the lower extremities with resultant of resting pain and eventually, tissue loss. At present time, it is likely that proangiogenic stem cell therapy is anticipated as a promising therapeutic strategy in patients with CLI. However, a potential limitation of autologous cell therapy is that the insufficient number of stem cells were available the patients who may also suffer other problems. Therefore, how to generate enough autologous stem cells in vitro for future implantation application has become a major issue. Cilostazol is used as a vasodilating and anti-platelet aggregation drug clinically by increasing intracellular levels of cAMP. Our recent works and other reports have suggested that cilostazol may promote angiogenesis. Unfortunately, the effects of cilostazol on growth and differentiation of human early endothelial progenitor cells (EPCs) remain mostly unclear. In the current work, we explored the novel angiogenic effects of cilostazol on EPCs by using both in vitro and in vivo models. We found that human early EPCs treated with cilostazol significantly increase colony-forming units and enhanced differentiation of EPCs toward endothelial lineage. It was not only stimulated proliferation, migration, anti-apoptosis effect but also in vitro vascular tube formation through activation of SDF-1α /CXCR4/PI3K/Akt signaling pathway. In addition, Matrigel plug assay and mouse hind limb ischemia model also demonstrated that administration of a concomitant therapy with cilostazol and EPCs-treated mice were in vessel maturation higher, capillary significantly density and blood flow recovery, in comparison with either treatment alone. These results indicated that co-administration of cilostazol reinforced the autocrine effect of transplanted human early EPCs to provide a synergistic effect in angiogenesis through activation of SDF-1 α/CXCR4/PI3K/Akt signaling pathway. In clinical Implication, cilostazol plus EPCs treatment may be beneficial in improving EPC transplantation efficacy and enhancing vascular re-endothelialization in patients with critical limb ischemia.
    Advisory Committee
  • Wang, Hay-Yan - chair
  • Li, Yi-Heng - co-chair
  • Wang, Yang-Kao - co-chair
  • Chen, Chun-Lin - co-chair
  • Cho, Chung-Lung - advisor
  • Chao, Ting-Hsing - advisor
  • Files
  • etd-0216117-100714.pdf
  • Indicate in-campus at 3 year and off-campus access at 5 year.
    Date of Submission 2017-03-21

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