open access

Vol 26, No 3 (2019)
Original articles — Basic science and experimental cardiology
Published online: 2018-03-26
Get Citation

Prevention of in-stent restenosis with endothelial progenitor cell (EPC) capture stent placement combined with regional EPC transplantation: An atherosclerotic rabbit model

You-Hua Huang, Qiang Xu, Tao Shen, Jian-Ke Li, Jing-Yu Sheng, Hong-Jian Shi
DOI: 10.5603/CJ.a2018.0027
·
Pubmed: 29611172
·
Cardiol J 2019;26(3):283-291.

open access

Vol 26, No 3 (2019)
Original articles — Basic science and experimental cardiology
Published online: 2018-03-26

Abstract

Background: Even with drug-eluting stents, the risk of in-stent restenosis (ISR) remains high. The goal of this study was to investigate the use of an endothelial progenitor cell (EPC) capture stent plus regional EPC transplantation to reduce the ISR rate.

Methods: Endothelial progenitor cell capture stents were fabricated using fibrin gel and anti-CD34 plus anti-VEGFR-2 dual antibodies. Twenty male New Zealand white rabbits established as an atherosclerotic model were randomly divided into two groups: group 1 (n = 10), in which EPC capture stents were deployed into the right iliac artery; and group 2 (n = 10), in which sirolimus-eluting stents were placed. In both groups, EPCs were transplanted into target vessels beyond the stents, with outflow blocked. Radiologic-pathologic correlation outcomes were reviewed after 2 months. 

Results: The technical success rate of EPC capture stent placement plus EPC transplantation was 100%. The ISR rate in group 1 was lower than in group 2 (1/10 vs. 4/10; p > 0.05). Minimal luminal diameters were larger in group 1 than in group 2 (computed tomographic angiography, 1.85 ± 0.15 mm vs. 1.50 ± 0.20 mm; duplex ultrasound, 1.90 ± 0.10 mm vs. 1.70 ± 0.30 mm; p > 0.05). Transplanted EPCs were tracked positively only in group 1. Pathologic analysis demonstrated neointimal hyperplasia thickness of 0.21 ± 0.09 mm in group 1 vs. 0.11 ± 0.07 mm in group 2 (p < 0.05). 

Conclusion: Endothelial progenitor cell capture stent placement plus local EPC transplant decreases the ISR rate through thrombosis reduction rather than through neointimal hyperplasia inhibition.

Abstract

Background: Even with drug-eluting stents, the risk of in-stent restenosis (ISR) remains high. The goal of this study was to investigate the use of an endothelial progenitor cell (EPC) capture stent plus regional EPC transplantation to reduce the ISR rate.

Methods: Endothelial progenitor cell capture stents were fabricated using fibrin gel and anti-CD34 plus anti-VEGFR-2 dual antibodies. Twenty male New Zealand white rabbits established as an atherosclerotic model were randomly divided into two groups: group 1 (n = 10), in which EPC capture stents were deployed into the right iliac artery; and group 2 (n = 10), in which sirolimus-eluting stents were placed. In both groups, EPCs were transplanted into target vessels beyond the stents, with outflow blocked. Radiologic-pathologic correlation outcomes were reviewed after 2 months. 

Results: The technical success rate of EPC capture stent placement plus EPC transplantation was 100%. The ISR rate in group 1 was lower than in group 2 (1/10 vs. 4/10; p > 0.05). Minimal luminal diameters were larger in group 1 than in group 2 (computed tomographic angiography, 1.85 ± 0.15 mm vs. 1.50 ± 0.20 mm; duplex ultrasound, 1.90 ± 0.10 mm vs. 1.70 ± 0.30 mm; p > 0.05). Transplanted EPCs were tracked positively only in group 1. Pathologic analysis demonstrated neointimal hyperplasia thickness of 0.21 ± 0.09 mm in group 1 vs. 0.11 ± 0.07 mm in group 2 (p < 0.05). 

Conclusion: Endothelial progenitor cell capture stent placement plus local EPC transplant decreases the ISR rate through thrombosis reduction rather than through neointimal hyperplasia inhibition.

Get Citation

Keywords

in-stent restenosis; thrombosis; endothelial progenitor cells; transplantation; drug-eluting stent

About this article
Title

Prevention of in-stent restenosis with endothelial progenitor cell (EPC) capture stent placement combined with regional EPC transplantation: An atherosclerotic rabbit model

Journal

Cardiology Journal

Issue

Vol 26, No 3 (2019)

Pages

283-291

Published online

2018-03-26

DOI

10.5603/CJ.a2018.0027

Pubmed

29611172

Bibliographic record

Cardiol J 2019;26(3):283-291.

Keywords

in-stent restenosis
thrombosis
endothelial progenitor cells
transplantation
drug-eluting stent

Authors

You-Hua Huang
Qiang Xu
Tao Shen
Jian-Ke Li
Jing-Yu Sheng
Hong-Jian Shi

References (42)
  1. Mozaffarian D, Benjamin EJ, Go AS, et al. American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics: 2015 update: a report from the American Heart Association. Circulation. 2015; 131(4): e29–322.
  2. Serruys PW, Kutryk MJB, Ong ATL. Coronary-artery stents. N Engl J Med. 2006; 354(5): 483–495.
  3. 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.
  4. Cosgrave J, Agostoni P, Ge L, et al. Clinical outcome following aleatory implantation of paclitaxel-eluting or sirolimus-eluting stents in complex coronary lesions. Am J Cardiol. 2005; 96(12): 1663–1668.
  5. Stone GW, Ellis SG, Cannon L, et al. TAXUS V Investigators. Comparison of a polymer-based paclitaxel-eluting stent with a bare metal stent in patients with complex coronary artery disease: a randomized controlled trial. JAMA. 2005; 294(10): 1215–1223.
  6. Cassese S, Byrne RA, Tada T, et al. Incidence and predictors of restenosis after coronary stenting in 10 004 patients with surveillance angiography. Heart. 2014; 100(2): 153–159.
  7. Sun Y, Li L, Su Q, et al. Comparative efficacy and safety of drug-eluting stent and conventional therapies in coronary heart disease patients with in-stent restenosis: a meta-analysis. Cell Biochem Biophys. 2014; 68(1): 211–229.
  8. Unverdorben M, Vallbracht C, Cremers B, et al. Paclitaxel-coated balloon catheter versus paclitaxel-coated stent for the treatment of coronary in-stent restenosis. Circulation. 2009; 119(23): 2986–2994.
  9. Holmes DR, Kereiakes DJ, Garg S, et al. Stent thrombosis. J Am Coll Cardiol. 2010; 56(17): 1357–1365.
  10. Tsigkas GG, Karantalis V, Hahalis G, et al. Stent restenosis, pathophysiology and treatment options: a 2010 update. Hellenic J Cardiol. 2011; 52(2): 149–157.
  11. Collins MJ, Li X, Lv W, et al. Therapeutic strategies to combat neointimal hyperplasia in vascular grafts. Expert Rev Cardiovasc Ther. 2012; 10(5): 635–647.
  12. Byrne RA, Neumann FJ, Mehilli J, et al. ISAR-DESIRE 3 investigators. Paclitaxel-eluting balloons, paclitaxel-eluting stents, and balloon angioplasty in patients with restenosis after implantation of a drug-eluting stent (ISAR-DESIRE 3): a randomised, open-label trial. Lancet. 2013; 381(9865): 461–467.
  13. Razavi MK, Mustapha JA, Miller LE. Contemporary systematic review and meta-analysis of early outcomes with percutaneous treatment for infrapopliteal atherosclerotic disease. J Vasc Interv Radiol. 2014; 25(10): 1489–96, 1496.e1.
  14. Bosiers M, Deloose K, Callaert J, et al. Superiority of stent-grafts for in-stent restenosis in the superficial femoral artery: twelve-month results from a multicenter randomized trial. J Endovasc Ther. 2015; 22(1): 1–10.
  15. Dippel EJ, Makam P, Kovach R, et al. EXCITE ISR Investigators. Randomized controlled study of excimer laser atherectomy for treatment of femoropopliteal in-stent restenosis: initial results from the EXCITE ISR trial (EXCImer Laser Randomized Controlled Study for Treatment of FemoropopliTEal In-Stent Restenosis). JACC Cardiovasc Interv. 2015; 8(1 Pt A): 92–101.
  16. 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.
  17. Sharif F, Hynes SO, Cooney R, et al. Gene-eluting stents: adenovirus-mediated delivery of eNOS to the blood vessel wall accelerates re-endothelialization and inhibits restenosis. Mol Ther. 2008; 16(10): 1674–1680.
  18. Walter DH, Cejna M, Diaz-Sandoval L, et al. Local gene transfer of phVEGF-2 plasmid by gene-eluting stents: an alternative strategy for inhibition of restenosis. Circulation. 2004; 110(1): 36–45.
  19. Blindt R, Vogt F, Astafieva I, et al. A novel drug-eluting stent coated with an integrin-binding cyclic Arg-Gly-Asp peptide inhibits neointimal hyperplasia by recruiting endothelial progenitor cells. J Am Coll Cardiol. 2006; 47(9): 1786–1795.
  20. Strehlow K, Werner N, Berweiler J, et al. Estrogen increases bone marrow-derived endothelial progenitor cell production and diminishes neointima formation. Circulation. 2003; 107(24): 3059–3065.
  21. Egashira K, Nakano K, Ohtani K, et al. Local delivery of anti-monocyte chemoattractant protein-1 by gene-eluting stents attenuates in-stent stenosis in rabbits and monkeys. Arterioscler Thromb Vasc Biol. 2007; 27(12): 2563–2568.
  22. Garg R, Tellez A, Alviar C, et al. The effect of percutaneous coronary intervention on inflammatory response and endothelial progenitor cell recruitment. Catheter Cardiovasc Interv. 2008; 72(2): 205–209.
  23. Miglionico M, Patti G, D'Ambrosio A, et al. Percutaneous coronary intervention utilizing a new endothelial progenitor cells antibody-coated stent: a prospective single-center registry in high-risk patients. Catheter Cardiovasc Interv. 2008; 71(5): 600–604.
  24. den Dekker WK, Houtgraaf JH, Onuma Y, et al. Final results of the HEALING IIB trial to evaluate a bio-engineered CD34 antibody coated stent (Genous™Stent) designed to promote vascular healing by capture of circulating endothelial progenitor cells in CAD patients. Atherosclerosis. 2011; 219(1): 245–252.
  25. Klomp M, Damman P, Beijk MAM, et al. Applying the National Institute for Clinical Excellence criteria to patients treated with the Genous™ Bio-engineered R stent™: a sub-study of the e-HEALING (Healthy Endothelial Accelerated Lining Inhibits Neointimal Growth) worldwide registry. Heart Vessels. 2012; 27(4): 360–369.
  26. Cassese S, Galasso G, Sciahbasi A, et al. Antiplatelet theRapy after Genous EPC-capturing coroNary stenT implantatiOn: the ARGENTO study: a prospective, multicenter registry. Int J Cardiol. 2013; 167(3): 757–761.
  27. Mai XL, Ma ZL, Sun JH, et al. Assessments of proliferation capacity and viability of New Zealand rabbit peripheral blood endothelial progenitor cells labeled with superparamagnetic particles. Cell Transplant. 2009; 18(2): 171–181.
  28. Li Na, Yang H, Lu L, et al. Comparison of the labeling efficiency of BrdU, DiI and FISH labeling techniques in bone marrow stromal cells. Brain Res. 2008; 1215: 11–19.
  29. Falk E. Pathogenesis of Atherosclerosis. J Am Coll Cardiol. 2006; 47(8 Suppl): C7–C12.
  30. Imamura H, Ohta T, Tsunetoshi K, et al. Transdifferentiation of bone marrow-derived endothelial progenitor cells into the smooth muscle cell lineage mediated by tansforming growth factor-beta1. Atherosclerosis. 2010; 211(1): 114–121.
  31. Xu BY, Xiang MX, Wang Ja. Endothelial Progenitor Cells and In-stent Restenosis. Curr Stem Cell Res Ther. 2015; 10(4): 364–371.
  32. Asahara T, Murohara T, Sullivan A, et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science. 1997; 275(5302): 964–967.
  33. Shi HJ, Cao AH, Chen J, et al. Transjugular intrahepatic portosystemic shunt with an autologous endothelial progenitor cell seeded stent: a porcine model. Acad Radiol. 2010; 17(3): 358–367.
  34. Shi HJ, Cao AH, Teng GJ. Seeding endothelial progenitor cells on a self-expanding metal stent: an in vitro study. J Vasc Interv Radiol. 2010; 21(7): 1061–1065.
  35. Marsboom G, Janssens S. Endothelial progenitor cells: new perspectives and applications in cardiovascular therapies. Expert Rev Cardiovasc Ther. 2008; 6(5): 687–701.
  36. Centemero MP, Stadler JR. Stent thrombosis: an overview. Expert Rev Cardiovasc Ther. 2012; 10(5): 599–615.
  37. Kim MS, Dean LS. In-stent restenosis. Cardiovasc Ther. 2011; 29(3): 190–198.
  38. Farooq V, Gogas BD, Serruys PW. Restenosis: delineating the numerous causes of drug-eluting stent restenosis. Circ Cardiovasc Interv. 2011; 4(2): 195–205.
  39. Fusaro M, Cassese S, Ndrepepa G, et al. Drug-eluting stents for revascularization of infrapopliteal arteries: updated meta-analysis of randomized trials. JACC Cardiovasc Interv. 2013; 6(12): 1284–1293.
  40. Alfonso F, Pérez-Vizcayno M, Cárdenas A, et al. A prospective randomized trial of Drug-Eluting balloons versus everolimus-eluting stents in patients with in-stent restenosis of drug-eluting stents. J Am Coll Cardiol. 2015; 66(1): 23–33.
  41. Spaulding C, Daemen J, Boersma E, et al. A pooled analysis of data comparing sirolimus-eluting stents with bare-metal stents. N Engl J Med. 2007; 356(10): 989–997.
  42. Kaiser C, Galatius S, Erne P, et al. BASKET–PROVE Study Group. Drug-eluting versus bare-metal stents in large coronary arteries. N Engl J Med. 2010; 363(24): 2310–2319.

Important: This website uses cookies. More >>

The cookies allow us to identify your computer and find out details about your last visit. They remembering whether you've visited the site before, so that you remain logged in - or to help us work out how many new website visitors we get each month. Most internet browsers accept cookies automatically, but you can change the settings of your browser to erase cookies or prevent automatic acceptance if you prefer.

By "Via Medica sp. z o.o." sp.k., ul. Świętokrzyska 73, 80–180 Gdańsk, Poland
tel.:+48 58 320 94 94, fax:+48 58 320 94 60, e-mail: viamedica@viamedica.pl