Specificity to capture endothelial progenitor cells in the peripheral blood by CD34 antibody applied on a rapamycin eluting stent

doi:10.3969/j.issn.2095-4344.2015.41.024

Abstract

Abstract:

BACKGROUND: Drug eluting stents and endothelium stents for clinical treatment of vascular stenosis can lead to delayed endothelialization and restenosis. A rapamycin eluting stent combined with CD34 antibody can play a synergistic role to offset delayed endothelialization and intimal hyperplasia due to antiproliferative drugs, but it is still in the pilot phase.
OBJECTIVE: To observe the ability of rapamycin eluting stent combined with CD34 antibody to capture endothelial progenitor cells, and to observe the differentiation characteristics of the captured cells.
METHODS: Scanning electron microscope and indirect immunofluorescence were used to observe the morphology and differentiation characteristics of captured endothelial progenitor cells. Under a fluorescence microscope, we observed the captured endothelial progenitor cells and the degree of endothelialization after implantation of the rapamycin eluting stent combined with CD34 antibody into rabbit ear vein.
RESULTS AND CONCLUSION: Under the scanning electron microscope, fusiform-like cells with a diameter of 6-8 μm were captured by the composite stent, and 24 hours later, the cells became full-shaped. The captured cells had the appearance characteristics of endothelial progenitor cells. Results from indirect immunofluorescence observation showed that there were a lot of red fluorescent spots on the coating which represented adherent cells positive for vascular endothelial growth factor receptor-2; the composite stent was largely covered with vascular endothelial cells at 24 hours after stent implantation, and fully covered at 48 hours, but there was no abnormal cell cluster. These findings indicate that the rapamycin eluting stent combined with CD34 antibody can be specific to rapidly capture endothelial progenitor cells in the peripheral blood, and the stent can be completely covered with vascular endothelial cells at 48 hours after stent implantation, thereby achieving rapid endothelialization and promoting the repair of endothelial cells.
中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

Key words: Sirolimus, Drug-Eluting Stents, Endothelial Cells, Vascular Endothelial Growth Factor Receptor-2, Tissue Engineering

Yang Feng, Zhao Qian, Zhang Shi-xuan, Zhao Tie-nan, Feng Bo. Specificity to capture endothelial progenitor cells in the peripheral blood by CD34 antibody applied on a rapamycin eluting stent[J]. Chinese Journal of Tissue Engineering Research, 2015, 19(41): 6694-6698.

Figures/Tables 3

References

[1] Williams DO, Holubkov R, Yeh W, et al. Percutaneous coronary intervention in the current era compared with 1985-1986: the National Heart, Lung, and Blood Institute Registries.Circulation. 2000;102(24):2945-2951.

[2] Ardissino D, Cavallini C, Bramucci E, et al. Sirolimus-eluting vs uncoated stents for prevention of restenosis in small coronary arteries: a randomized trial. JAMA. 2004;292(22): 2727-2734.

[3] Carter AJ, Aggarwal M, Kopia GA, et al. Long-term effects of polymer-based, slow-release, sirolimus-eluting stents in a porcine coronary model. Cardiovasc Res. 2004;63(4): 617-624.

[4] Pfisterer M, Brunner-La Rocca HP, Buser PT, et al. Late clinical events after clopidogrel discontinuation may limit the benefit of drug-eluting stents: an observational study of drug-eluting versus bare-metal stents. J Am Coll Cardiol. 2006;48(12):2584-2591.

[5] Nordmann AJ, Briel M, Bucher HC. Mortality in randomized controlled trials comparing drug-eluting vs. bare metal stents in coronary artery disease: a meta-analysis. Eur Heart J. 2006;27(23):2784-2814.

[6] Camenzind E, Steg PG, Wijns W. Stent thrombosis late after implantation of first-generation drug-eluting stents: a cause for concern. Circulation. 2007;115(11):1440-1455.

[7] Joner M, Finn AV, Farb A, et al. Pathology of drug-eluting stents in humans: delayed healing and late thrombotic risk. J Am Coll Cardiol. 2006;48(1):193-202.

[8] Kong D, Melo LG, Mangi AA, et al. Enhanced inhibition of neointimal hyperplasia by genetically engineered endothelial progenitor cells. Circulation. 2004;109(14):1769-1775.

[9] 谭强,邱录贵,李广平,等.循环早期内皮祖细胞与外向生长内皮细胞在血管新生中的作用[J].中华高血压杂志,2010,18(7): 658-664.

[10] Kutryk MJ, Kuliszewski MA. In vivo endothelial progenitor cell seeding of stented Arterial segments and vascular grafts. Circulation. 2003; 108(suppl IV): IV-573.

[11] Schober A, Hoffmann R, Oprée N, et al. Peripheral CD34+ cells and the risk of in-stent restenosis in patients with coronary heart disease. Am J Cardiol. 2005;96(8):1116-1122.

[12] Berger J, Reist M, Mayer JM, et al. Structure and interactions in chitosan hydrogels formed by complexation or aggregation for biomedical applications. Eur J Pharm Biopharm. 2004; 57(1):35-52.

[13] Ueno H, Mori T, Fujinaga T. Topical formulations and wound healing applications of chitosan. Adv Drug Deliv Rev. 2001; 52(2):105-115.

[14] 尹青令,侯宁宁,崔晓栋,等.聚乳酸防粘连膜对晚期内皮祖细胞功能的影响[J].功能材料,2014,45(3):3101-3105.

[15] Hristov M, Weber C. Endothelial progenitor cells in vascular repair and remodeling. Pharmacol Res. 2008;58(2):148-151.

[16] 崔斌,黄岚,宋耀明,等. 冠心病患者循环内皮祖细胞与相关危险因素及冠状动脉病变的关系[J].中华心血管病杂志,2013,33(9): 785-788.

[17] 张峰,郭伟,余占江,等. 对用于包被冠状动脉支架的抗CD34单克隆抗体的生物学指标的质量控制研究[J].药物分析杂志,2011, 31(5):862-866.

[18] Rodriguez AE. Emerging drugs for coronary restenosis: the role of systemic oral agents the in stent era. Expert Opin Emerg Drugs. 2009;14(4):561-576.

[19] Celik T, Iyisoy A, Kursaklioglu H,et al. The forgotten player of in-stent restenosis: endothelial dysfunction. Int J Cardiol. 2008;126(3):443-444.

[20] Joner M, Finn AV, Farb A, et al. Pathology of drug-eluting stents in humans: delayed healing and late thrombotic risk. J Am Coll Cardiol. 2006;48(1):193-202.

[21] Dangas GD, Claessen BE, Caixeta A, et al. In-stent restenosis in the drug-eluting stent era. J Am Coll Cardiol. 2010;56(23):1897-1907.

[22] Asahara T, Murohara T, Sullivan A, et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science. 1997; 275(5302):964-967.

[23] Chen JP. Safety and efficacy of the drug-eluting stent: a double-edged sword. South Med J. 2008;101(2):174-178.

[24] Takano M, Yamamoto M, Xie Y, et al. Serial long-term evaluation of neointimal stent coverage and thrombus after sirolimus-eluting stent implantation by use of coronary angioscopy. Heart. 2007;93(11):1353-1356.

[25] 郜俊清,金惠根,严鹏勇,等.壳聚糖/肝素雷帕霉素药物洗脱支架对猪冠状动脉早期快速内皮化及抗血栓的作用[J].中国循环杂志,2013,28(3):218-221.

[26] Aoki J, Serruys PW, van Beusekom H, et al. Endothelial progenitor cell capture by stents coated with antibody against CD34: the HEALING-FIM (Healthy Endothelial Accelerated Lining Inhibits Neointimal Growth-First In Man) Registry. J Am Coll Cardiol. 2005;45(10):1574-1579.

Nakazawa G, Granada JF, Alviar CL, et al. Anti-CD34 antibodies immobilized on the surface of sirolimus-eluting stents enhance stent endothelialization. JACC Cardiovasc Interv. 2010;3(1):68-75.