title: Mobilization of CD34-positive bone marrow-derived cells after coronary stent implantation: impact on restenosis.
abstract: BACKGROUND
  Recently, accumulating evidence has indicated that bone marrow-derived stem cells are capable of differentiating into vascular cells. It has been hypothesized that the inflammatory response after vascular injury triggers the mobilization of endothelial and smooth muscle progenitor cells from bone marrow.
  
  
  RESULTS
  We measured circulating CD34-positive mononuclear cells, activation of integrin Mac-1 on the surface of neutrophils, and plasma granulocyte-colony stimulating factor levels in 40 patients undergoing coronary stenting. After bare-metal stenting, CD34-positive cells increased, reaching a maximum on day 7 after stenting. The maximum change compared with baseline before stenting was more striking in patients with restenosis than without restenosis (332+/-108% versus 148+/-49%; P<0.05). In contrast, CD34-positive cells decreased after sirolimus-eluting stenting (72+/-21% on day 7). The change in CD34-positive cells on day 7 relative to baseline was closely correlated with that in activated Mac-1 at 48 hours (R=0.52, P<0.01) and that in granulocyte-colony stimulating factor levels at 24 hours (R=0.42, P<0.05). Cell culture assay on day 7 showed that mononuclear cells differentiated into CD31-positive endothelium-like cells after bare-metal stenting. In patients with restenosis, mononuclear cells differentiating into alpha-smooth muscle actin-positive smooth muscle-like cells also were observed. Implantation of sirolimus-eluting stents suppressed both types of differentiation.
  
  
  CONCLUSIONS
  Stent implantation may induce differentiation of bone marrow cells into endothelial or smooth muscle cells. Endothelial cells may participate in reendothelialization, a protective reaction against vascular injury, whereas smooth muscle cells may participate in neointimal thickening and restenosis. Sirolimus-eluting stents appear to inhibit the mobilization and differentiation of bone marrow cells.
authors.affiliation: Department of Cardiovascular and Renal Medicine, Saga University Faculty of Medicine, 5-1-1 Nabeshima, Saga 849-8501, Japan. inouete@med.saga-u.ac.jp
authors.forename: Teruo
authors.initials: T
authors.lastname: Inoue
authors.forename: Masataka
authors.initials: M
authors.lastname: Sata
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Hikichi
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Sohma
authors.forename: Daiju
authors.initials: D
authors.lastname: Fukuda
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Uchida
authors.forename: Minoru
authors.initials: M
authors.lastname: Shimizu
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Komoda
authors.forename: Koichi
authors.initials: K
authors.lastname: Node
mesh_terms: D000368:Aged; D018952:Antigens, CD34 / Q000097:blood*; D001854:Bone Marrow Cells / Q000166:cytology* / Q000502:physiology; D006328:Cardiac Catheterization / Q000009:adverse effects; D002465:Cell Movement / Q000502:physiology; D003324:Coronary Artery Disease / Q000097:blood / Q000628:therapy; D023903:Coronary Restenosis / Q000097:blood* / Q000209:etiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015607:Stents / Q000009:adverse effects*; D013997:Time Factors
chemical_list: D018952:Antigens, CD34