Cells of primarily extravascular origin in neointima formation following stent implantation: coordinated expression of endothelial progenitor, dendritic and neural crest-derived cells.
OBJECTIVE
In-stent restenosis due to neointima formation is a major limitation following stent implantation. Recently, several studies reported mobilization of primarily extravascular cells to the arterial sites after balloon angioplasty. Therefore, the goal of the present study was to assess the coordinated neointimal expression of endothelial progenitor, dendritic and neural crest-derived cells after stent implantation.


METHODS
Male minipigs underwent stent implantation in abdominal aortic segments. Animals were sacrificed at 1, 7, 14, 30, 60 or 90 days. Cross sections of the injured vessels were obtained for immunohistochemistry using specific antibodies for the detection of endothelial progenitor (CD133), dendritic (S100) and neural crest-derived cells (GFAP), as well as monocytes/macrophages (CD14) and T lymphocytes (CD3).


RESULTS
As a key finding, frequency of CD133, S100, GFAP, CD14 and CD3 (18.5 +/- 3.6, 14.9 +/- 1.8, 10.6 +/- 1.1, 40.2 +/- 8.3 and 5.0 +/- 0.6%, respectively) in neointima was maximal at day 7. With ongoing neointima enlargement, expression of these cells decreased. In advanced neointima, labeled cells were predominantly localized at luminal and stented sites. Media showed almost no immunoreactivity of the markers studied, whereas adventitial zones of neovascularization revealed some signals.


CONCLUSIONS
Endothelial progenitor, dendritic, neural crest-derived and inflammatory cells are consistently recruited into arterial neointima, mostly at early time points after stent implantation.
Department of Internal Medicine II - Cardiology, University of Bonn, Bonn, Germany.
Izabela
I
Tuleta
Dirk
D
Skowasch
Matthias
M
Peuster
Georg
G
Nickenig
Gerhard
G
Bauriedel
D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D001012:Aorta, Abdominal; D017252:CD3 Complex / Q000032:analysis; D003713:Dendritic Cells / Q000145:classification / Q000473:pathology*; D042783:Endothelial Cells / Q000145:classification / Q000473:pathology*; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D006023:Glycoproteins / Q000032:analysis; D007150:Immunohistochemistry; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D008297:Male; D010455:Peptides / Q000032:analysis; D009418:S100 Proteins / Q000032:analysis; D013234:Stem Cells / Q000145:classification / Q000473:pathology*; D015607:Stents; D013552:Swine; D013556:Swine, Miniature; D017539:Tunica Intima / Q000473:pathology* / Q000503:physiopathology
D000071916:AC133 Antigen; D015703:Antigens, CD; D017252:CD3 Complex; D005904:Glial Fibrillary Acidic Protein; D006023:Glycoproteins; D018950:Lipopolysaccharide Receptors; D010455:Peptides; D009418:S100 Proteins