scholarly journals Cilostazol Improves Proangiogenesis Functions in Human Early Endothelial Progenitor Cells through the Stromal Cell-Derived Factor System and Hybrid Therapy Provides a Synergistic EffectIn Vivo

2016 ◽  
Vol 2016 ◽  
pp. 1-18 ◽  
Author(s):  
Shih-Ya Tseng ◽  
Ting-Hsing Chao ◽  
Yi-Heng Li ◽  
Chung-Lung Cho
Keyword(s):  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Stromal Cell ◽  
Ex Vivo ◽  
Akt Signaling ◽  
Endothelial Progenitor ◽  
Hybrid Therapy ◽  
Stromal Cell Derived Factor

This study investigated the effect of cilostazol on proangiogenesis functions in human early endothelial progenitor cells (EPCs)in vitroand the therapeutic implication of hybrid therapy with cilostazol and human early EPCsin vivo. Cilostazol significantly increased colony-forming units and enhanced differentiation of EPCs toward endothelial lineage. Treatments resulted in antiapoptotic effects and stimulated proliferation and migration andin vitrovascular tube formation through activation of stromal cell-derived factor-1 (SDF-1)/C-X-C chemokine receptor type 4 (CXCR4)/phosphatidylinositol-3 kinase (PI3K)/Akt signaling pathway. Blood flow recovery and capillary density in murine ischemic hindlimbs were significantly improved in cilostazol-treated, human early EPCs-treated, and cotreatment groups. The effects were attenuated with SDF-1αinhibition. Plasma SDF-1αlevels were significantly higher in 3 active treatment groups after surgery, with greatest effects observed in hybrid therapy. The angiogenic effects of transplanted EPCs pretreated with cilostazolex vivowere superior to untreated EPCs usingin vivoMatrigel assay. Implanted EPCs were incorporated into the capillary, with pretreatment or cotreatment with cilostazol resulting in enhanced effects. Taken together, cilostazol promotes a large number of proangiogenic functions in human early EPCs through activation of SDF-1/CXCR4/PI3K/Akt signaling, and hybrid therapy provides a synergistic effectin vivo. Cotreatment may be beneficial in ischemic disease.

scholarly journals Role of β2-integrins for homing and neovascularization capacity of endothelial progenitor cells

2004 ◽  
Vol 201 (1) ◽  
pp. 63-72 ◽  
Author(s):  
Emmanouil Chavakis ◽  
Alexandra Aicher ◽  
Christopher Heeschen ◽  
Ken-ichiro Sasaki ◽  
Ralf Kaiser ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Ex Vivo ◽  
Limb Ischemia ◽  
Endothelial Progenitor ◽  
Cell Monolayers ◽  
Β2 Integrins

The mechanisms of homing of endothelial progenitor cells (EPCs) to sites of ischemia are unclear. Here, we demonstrate that ex vivo–expanded EPCs as well as murine hematopoietic Sca-1+/Lin− progenitor cells express β2-integrins, which mediate the adhesion of EPCs to endothelial cell monolayers and their chemokine-induced transendothelial migration in vitro. In a murine model of hind limb ischemia, Sca-1+/Lin− hematopoietic progenitor cells from β2-integrin–deficient mice are less capable of homing to sites of ischemia and of improving neovascularization. Preactivation of the β2-integrins expressed on EPCs by activating antibodies augments the EPC-induced neovascularization in vivo. These results provide evidence for a novel function of β2-integrins in postnatal vasculogenesis.

Abstract 3955: Chemokines Fused to a Fractalkine Backbone and a GPI-Anchor Attract Embryonic Endothelial Progenitor Cells to the Site of Ischemia

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Chiraz El-Aouni ◽  
Franziska Globisch ◽  
Achim Pfosser ◽  
Georg Stachel ◽  
Rabea Hinkel ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Adhesion Molecule ◽  
Capillary Density ◽  
Gpi Anchor ◽  
Endothelial Progenitor ◽  
Collateral Growth ◽  
Artificial Adhesion

Recruitment of endothelial progenitor cells to the sites of ischemia is a prerequisite for efficient therapeutic neovascularization via vasculogenesis. Chemokines play a major role in the homing of EPCs at the ischemic vasculature, a mechanism fading in chronic ischemia. To overcome this limitation, we constructed an artificial adhesion molecule consisting of a GPI-anchor, a fractalkine-backbone and an SDF-1 head (SDF-1-fra-GPI), which was applied for enhanced recruitment of embryonic EPCs (eEPCs: CXCR4++, Tie2++, Thrombomodulin++, CD34-, MHCI-, vWF inducible, eNOS inducible) in vitro and in vivo . Methods: In a flow chamber adhesion assay, Control plasmids (pcDNA or GPI-SDF-1 cDNA) were compared to the SDF-1-fra-GPI construct for eEPC recruitment 24h after liposomal transfection of rat endothelial cells. In vivo, in rabbits (n=5 per group) at day 7 (d7) after femoral artery excision, 1 mg of the SDF-1-fra-GPI or eGFP cDNA was transfected into the ischemic limb. At d9, ischemic hindlimbs were retroinfused with 5x10 6 eEPCs. Angiography was performed for collateral quantification and frame count score at d9 and d37 (% of d9), capillary density was assessed via PECAM-1-staining (capillaries/muscle fiber = c/mf). Results: In vitro, eEPC adhesion (16±12 cells/field) was increased to a higher extent by SDF-1-fra-GPI (79±13) than SDF1-GPI (54±8) or control vector (37±8). In vivo , eEPC adhesion in the ischemic hindlimb after SDF-1-fra-GPI transfection compared to mock transfection (30±3 vs. 9±1 cells/field). Whereas capillary density was unaffected (1.66±0.30 SDF-1-Fra-GPI vs. 1.56±0.29 eEPCs), collateral growth (152±10% SDF-1-fra-GPI vs. 124±13%) as well as perfusion score (198±17% SDF-1-fra-GPI vs.160±6% eEPCs) further increased after SDF-1-fra-GPI transfection (controls: 1.24±0.12 c/mf, collaterals 105±8%, perfusion score 112±11%). We conclude that recruitment of EPCs expressing CXCR4 (the SDF-1 receptor) may benefit from pre-treatment of the recipient vasculature with SDF-1-Fra-GPI, an artificial adhesion molecule. This approach might be valuable for enhancing EPC recruitment in the scenario of therapeutic neovascular-ization of chronic ischemic syndromes.

scholarly journals Exercise Induces Stromal Cell–Derived Factor-1α–Mediated Release of Endothelial Progenitor Cells with Increased Vasculogenic Function

2015 ◽  
Vol 135 (2) ◽  
pp. 340e-350e ◽  
Author(s):  
Edwin Chang ◽  
Josemaria Paterno ◽  
Dominik Duscher ◽  
Zeshaan N. Maan ◽  
Jerry S. Chen ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Stromal Cell ◽  
Endothelial Progenitor ◽  
Stromal Cell Derived Factor

scholarly journals Effects of androgens on endothelial progenitor cells in vitro and in vivo

2009 ◽  
Vol 117 (10) ◽  
pp. 355-364 ◽  
Author(s):  
Gian Paolo Fadini ◽  
Mattia Albiero ◽  
Andrea Cignarella ◽  
Chiara Bolego ◽  
Christian Pinna ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Endothelial Progenitor Cell ◽  
Cell Biology ◽  
Progenitor Cell ◽  
Adult Males ◽  
Endothelial Progenitor ◽  
Healthy Human

The beneficial or detrimental effects of androgens on the cardiovascular system are debated. Endothelial progenitor cells are bone-marrow-derived cells involved in endothelial healing and angiogenesis, which promote cardiovascular health. Oestrogens are potent stimulators of endothelial progenitor cells, and previous findings have indicated that androgens may improve the biology of these cells as well. In the present study, we show that testosterone and its active metabolite dihydrotestosterone exert no effects on the expansion and function of late endothelial progenitors isolated from the peripheral blood of healthy human adult males, whereas they positively modulate early ‘monocytic’ endothelial progenitor cells. In parallel, we show that castration in rats is followed by a decrease in circulating endothelial progenitor cells, but that testosterone and dihydrotestosterone replacement fails to restore endothelial progenitor cells towards normal levels. This is associated with persistently low oestrogen levels after androgen replacement in castrated rats. In a sample of 62 healthy middle-aged men, we show that circulating endothelial progenitor cell levels are more directly associated with oestradiol, rather than with testosterone, concentrations. In conclusion, our results collectively demonstrate that androgens exert no direct effects on endothelial progenitor cell biology in vitro and in vivo.

scholarly journals Platelet-Derived Stromal Cell–Derived Factor-1 Regulates Adhesion and Promotes Differentiation of Human CD34+Cells to Endothelial Progenitor Cells

Circulation ◽  
2008 ◽  
Vol 117 (2) ◽  
pp. 206-215 ◽  
Author(s):  
Konstantinos Stellos ◽  
Harald Langer ◽  
Karin Daub ◽  
Tanja Schoenberger ◽  
Alexandra Gauss ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Stromal Cell ◽  
Endothelial Progenitor ◽  
Human Cd34 ◽  
Cd34 Cells ◽  
Stromal Cell Derived Factor
Sign in / Sign up

Export Citation Format

Share Document