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Ischemia- and cytokine-induced mobilization of bone marrow-derived endothelial progenitor cells for neovascularization
Author(s): Takahashi T, Kalka C, Masuda H, Chen D, Silver M, Kearney M, Magner M, Isner JM, Asahara T
Source: NATURE MEDICINE    Volume: 5    Issue: 4    Pages: 434-438    Published: APR 1999  
Times Cited: 1,059     References: 18     
Abstract: Endothelial progenitor cells (EPCs) have been isolated from circulating mononuclear cells in human peripheral blood and shown to be incorporated into foci of neovascularization, consistent with postnatal vasculogenesis'. We determined whether endogenous stimuli (tissue ischemia) and exogenous cytokine therapy (granulocyte macrophage-colony stimulating factor, GM-CSF) mobilize EPCs and thereby contribute to neovascularization of ischemic tissues. The development of regional ischemia in both mice and rabbits increased the frequency of circulating EPCs. In mice, the effect of ischemia-induced EPC mobilization was demonstrated by enhanced ocular neovascularization after cornea micropocket surgery in mice with hindlimb ischemia compared with that in non-ischemic control mice. In rabbits with hindlimb ischemia, circulating EPCs were further augmented after pretreatment with CM-CSF, with a corresponding improvement in hindlimb neovascularization. There was direct evidence that EPCs that contributed to enhanced corneal neovascularization were specifically mobilized from the bone marrow in response to ischemia and GM-CSF in mice transplanted with bone marrow from transgenic donors expressing P-galactosidase transcriptionally regulated by the endothelial cell-specific Tie-2 promoter. These findings indicate that circulating EPCs are mobilized endogenously in response to tissue ischemia or exogenously by cytokine therapy and thereby augment neovascularization of ischemic tissues.
Document Type: Article
Language: English
Reprint Address: Isner, JM (reprint author), Tufts Univ, St Elizabeths Med Ctr, Sch Med, Dept Med Cardiol, 736 Cambridge St, Boston, MA 02135 USA
Addresses:
1. Tufts Univ, St Elizabeths Med Ctr, Sch Med, Dept Med Cardiol, Boston, MA 02135 USA
2. Tufts Univ, St Elizabeths Med Ctr, Sch Med, Dept Biomed Res, Boston, MA 02135 USA
Publisher: NATURE AMERICA INC, 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA
Subject Category: Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental
IDS Number: 183VG
ISSN: 1078-8956
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