Journal of Vascular and Interventional Radiology
Volume 20, Issue 12 , Pages 1617-1624, December 2009

Delivery Site of Perivascular Endothelial Cell Matrices Determines Control of Stenosis in a Porcine Femoral Stent Model

  • Helen M. Nugent, PhD

      Affiliations

    • Department of Research and Development, Pervasis Therapeutics, One Kendall Square, Bldg 600, 1st Fl, Cambridge, MA 02139
    • Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts
    • Corresponding Author InformationAddress correspondence to H.M.N.
    • ,
  • Yin-Shan Ng, PhD

      Affiliations

    • Department of Research and Development, Pervasis Therapeutics, One Kendall Square, Bldg 600, 1st Fl, Cambridge, MA 02139
    • ,
  • Desmond White, BS

      Affiliations

    • Department of Research and Development, Pervasis Therapeutics, One Kendall Square, Bldg 600, 1st Fl, Cambridge, MA 02139
    • ,
  • Adam Groothius, MS

      Affiliations

    • Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts
    • Concord BioMedical Sciences and Emerging Technologies, Lexington, Massachusetts
    • ,
  • Glenn Kanner, BS

      Affiliations

    • Department of Research and Development, Pervasis Therapeutics, One Kendall Square, Bldg 600, 1st Fl, Cambridge, MA 02139
    • ,
  • Elazer R. Edelman, MD, PhD

      Affiliations

    • Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts
    • Cardiovascular Division, Brigham and Women's Hospital, Department of Medicine, Harvard Medical School, Boston, Massachusetts

published online 26 October 2009.

Purpose

Endothelial cells, grown within gelatin matrices and implanted onto the adventitia of injured vessels, inhibit stenosis in experimental models. To determine if this technology could be adapted for minimally invasive procedures, the authors compared the effects of cells in an implantable sponge to that of an injectable formulation and investigated the importance of delivery site in a stent model.

Materials and Methods

Stents were implanted in the femoral arteries of 30 pigs. This was followed by perivascular implantation of sponges or injection of particles containing allogeneic endothelial cells. Controls received acellular matrices or nothing. The effects of delivery site were assessed by injecting cellular matrices into or adjacent to the perivascular tissue or into the neighboring muscle. Animals were sacrificed after 28 days. Pre-sacrifice angiograms and tissue sections were evaluated for stenosis.

Results

Arteries treated with cellular matrices had a 55%–63% decrease in angiographic stenosis (P < .05) and a 38%–43% reduction in histologic stenoses (P < .05) compared to controls. Intimal area was greatest when cellular matrices were delivered into the muscle (6.35 mm2 ± 0.95) rather than into or adjacent to the perivascular tissue (4.05 mm2 ± 0.56 and 4.73 mm2 ± 0.53, respectively; P < .05).

Conclusions

Perivascular endothelial cell matrices reduced stenosis after stent-induced injury. The effects were not dependent on the formulation but appeared to be dependent on delivery site. Minimally invasive injections of endothelial cell matrices to the adventitia of arteries following peripheral interventions may decrease restenosis rates.

Abbreviations: FGF-2, fibroblast growth factor, TGF-β1, transforming growth factor β1, TIMP-2, tissue inhibitor of metalloproteinase-2

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 H.M.N., Y.S.N., G.K., and D.W. are employees of and have shares in Pervasis Therapeutics. E.R.E. is on the board of directors and has shares in Pervasis Therapeutics. E.R.E. was supported by grants from USA National Institutes of Health (GM 49039). Research described in this article was supported by Pervasis Therapeutics. The other author has not identified a conflict of interest.

PII: S1051-0443(09)00882-3

doi:10.1016/j.jvir.2009.08.020

Journal of Vascular and Interventional Radiology
Volume 20, Issue 12 , Pages 1617-1624, December 2009

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