Effect Of The Stent Coated By Antibodoy To Mesenchymal Stem Cells On Coronary Artrty Emdothelial Repair In Canine Model With Balloon Injury

Objective: Endothelial coverage after coronary stenting is correlated with the occurrence of stent thrombosis. The present study aimed at investigating the effect of the stent coated by antibody to mesenchymal stem cells(MSCs) on coronary artery endothelial repair in canine model with balloon injury.Methods: Bone marrow was harvested from iliac puncture with 21 G needle.from domestic dogs MSCs were isolated by density gradient centrifugation and cultured in vitro. Prepar monoclonal antibody mouse anti-canine of MSCs and IgG Fab′fragments Bare metal stent was immersed in hydroxyethyl cellulose with ethanol for 60 min. per se, and then, was co-bathed in suspension comtaining mesenchymal stem cells antibody(IgG Fab, fragments)overnight. Coronary artery injury model by repeat balloon inflation with fixed length was built. MSCs antibody stents (n=20) was deployed at the distal segment of left anterior descending coronary artery, with the bare stents (n=20) in proximal portion of the same artery considered to be as control. MSCs suspension with 2×107cells/mL was slowly injected via the central lumen of over-the-wire balloon for 4 min.. Animals were monitored through the whole study immediatel after the record of baseline coronary angiogram(CAG) and intravascular ultrasound(IVUS). At 4 weeks post-procedure, animals were killed after repeat CAG and IVUS. Stented vessel was removed from the heart, and was analyzed by HE staining, immunohistochemistry and electron microscopy.Results: Stents were successfully implanted in 20 animals, with 4 dogs died within 2h. from ventricular fibrillation(n=1), bleeding(n=2), and anesthesia accident(n=1), respectively. The remaining 16 canines survived through the study. At 4 weeks post-procedure:①the minimal lumen diameter (MLD) in MSCs antibody stent group significantly decreased from3.26±0.21mm at baseline to3.08±0.13mm( -4.7±9.8%) , compared to bare stent group(from 3.41±0.24mm at baseline to3.00±0.19mm, -13.6±6.4%, P=0.035) ;②the minimal lumen area (MLA) (4.45±.0.10mm2) in MSCs antibody stent group significantly increased in relative to bare stent group(3.74±0.35 mm2 P=0.016);③the neointimal area (NIA) (2.27±0.46mm2)in MSCs antibody stent group was significantly different to bare stent group(2.97±0.70mm2 , P=0.032) ;④HE staining showed the MSCs antibody stent group significantly reduced the thickness of neointimal hyperplasia ,when comparing with cellulose stent group;⑤Finally immunohistochemistry and electron microscopy confirmed the differentiation of MSCs into endothelial cells , which promoted the endothelial coverage.Conclusion: Mesenchymal stem cells via conection with their specific antibody on the surface of bare metal stents has potential of repairing the endothelial injury, with resultant decreased neointimal hyperplasia.