title: Capture of circulatory endothelial progenitor cells and accelerated re-endothelialization of a bio-engineered stent in human ex vivo shunt and rabbit denudation model.
abstract: OBJECTIVE
  The Genous™ Bio-engineered R™ stent (GS) aims to promote vascular healing by capture of circulatory endothelial progenitor cells (EPCs) to the surface of the stent struts, resulting in accelerated re-endothelialization. Here, we assessed the function of the GS in comparison to bare-metal stent (BMS), when exposed to the human and animal circulation.
  
  
  RESULTS
  First, 15 patients undergoing coronary angiography received an extracorporeal femoral arteriovenous (AV) shunt containing BMS and GS. Macroscopical mural thrombi were observed in BMS, whereas GS remained visibly clean. Confocal and scanning electron microscopic (SEM) analysis of GS showed an increase in strut coverage. Quantitative polymerase chain reaction (qPCR) analysis of captured cells on the GS demonstrated increased expression of endothelial markers KDR/VEGFR2 and E-selectin, and a decrease in pro-thrombogenic markers tissue factor pathway inhibitor and plasminogen activator inhibitor-1 compared with BMS. Secondly, a similar primate AV shunt model was used to validate these findings and occlusion of BMS was observed, while GS remained patent, as demonstrated by live imaging of indium-labelled platelets. Thirdly, in an in vitro cell-capture assay, GS struts showed increased coverage by EPCs, whereas monocyte coverage remained similar to BMS. Finally, the assessment of re-endothelialization was studied in a rabbit denudation model. Twenty animals received BMS and GS in the aorta and iliac arteries for 7 days. Scanning electron microscopic analysis showed a trend towards increased strut coverage, confirmed by qPCR analysis revealing increased levels of endothelial markers (Tie2, CD34, PCD31, and P-selectin) in GS.
  
  
  CONCLUSIONS
  In this proof-of-concept study, we have demonstrated that the bio-engineered EPC-capture stent, Genous™ R™ stent, is effective in EPC capture, resulting in accelerated re-endothelialization and reduced thrombogenicity.
authors: Molecular Cardiology Laboratory, Ee2389a, Experimental Cardiology, Thoraxcenter,  Erasmus University Medical Center, 's-Gravendijkwal 230, 3015 GE Rotterdam,  The Netherlands.
authors: Katarína
authors: K
authors: Larsen
authors: Caroline
authors: C
authors: Cheng
authors: Dennie
authors: D
authors: Tempel
authors: Sherry
authors: S
authors: Parker
authors: Saami
authors: S
authors: Yazdani
authors: Wijnand K
authors: WK
authors: den Dekker
authors: Jaco H
authors: JH
authors: Houtgraaf
authors: Renate
authors: R
authors: de Jong
authors: Stijn
authors: S
authors: Swager-ten Hoor
authors: Erik
authors: E
authors: Ligtenberg
authors: Stephen R
authors: SR
authors: Hanson
authors: Steve
authors: S
authors: Rowland
authors: Frank
authors: F
authors: Kolodgie
authors: Patrick W
authors: PW
authors: Serruys
authors: Renu
authors: R
authors: Virmani
authors: Henricus J
authors: HJ
authors: Duckers
mesh_terms: D000368:Aged; D015906:Angioplasty, Balloon, Coronary / Q000379:methods; D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D001166:Arteriovenous Shunt, Surgical / Q000379:methods*; D057005:Bioengineering; D015415:Biomarkers / Q000378:metabolism; D006328:Cardiac Catheterization / Q000379:methods; D003324:Coronary Artery Disease / Q000628:therapy*; D023903:Coronary Restenosis / Q000517:prevention & control; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology; D005260:Female; D006083:Graft Occlusion, Vascular / Q000517:prevention & control; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000502:physiology; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D010215:Papio; D010973:Platelet Adhesiveness / Q000502:physiology; D011817:Rabbits; D013234:Stem Cells / Q000502:physiology*; D015607:Stents
chemical_list: D018952:Antigens, CD34; D015415:Biomarkers; D016207:Cytokines