title: Cooperation between human fibrocytes and endothelial colony-forming cells increases angiogenesis via the CXCR4 pathway.
abstract: Fibrotic diseases of the lung are associated with a vascular remodelling process. Fibrocytes (Fy) are a distinct population of blood-borne cells that co-express haematopoietic cell antigens and fibroblast markers, and have been shown to contribute to organ fibrosis. The purpose of this study was to determine whether fibrocytes cooperate with endothelial colony-forming cells (ECFC) to induce angiogenesis. We isolated fibrocytes from blood of patient with idiopathic pulmonary fibrosis (IPF) and characterised them by flow cytometry, quantitative reverse transcriptase PCR (RTQ-PCR), and confocal microscopy. We then investigated the angiogenic interaction between fibrocytes and cord-blood-derived ECFC, both in vitro and in an in vivo Matrigel implant model. Compared to fibroblast culture medium, fibrocyte culture medium increased ECFC proliferation and differentiation via the SDF-1/CXCR4 pathway. IPF-Fy co-implanted with human ECFC in Matrigel plugs in immunodeficient mice formed functional microvascular beds, whereas fibroblasts did not. Evaluation of implants after two weeks revealed an extensive network of erythrocyte-containing blood vessels. CXCR4 blockade significantly inhibited this blood vessel formation. The clinical relevance of these data was confirmed by strong CXCR4 expression in vessels close to fibrotic areas in biopsy specimens from patients with IPF, by comparison with control lungs. In conclusion, circulating fibrocytes might contribute to the intense remodelling of the pulmonary vasculature in patients with idiopathic pulmonary fibrosis.
authors.affiliation: Prof. David Smadja, Paris-Descartes University, INSERM UMR-S 1140, Hematology department, European Georges Pompidou hospital, 20 rue Leblanc, 75015 Paris, France, Tel.: +33 1 56093933, Fax: +33 1 56093393, E-mail: david.smadja@egp.aphp.fr.
authors.forename: David M
authors.initials: DM
authors.lastname: Smadja
authors.forename: Peter
authors.initials: P
authors.lastname: Dorfmüller
authors.forename: Coralie L
authors.initials: CL
authors.lastname: Guerin
authors.forename: Ivan
authors.initials: I
authors.lastname: Bieche
authors.forename: Cécile
authors.initials: C
authors.lastname: Badoual
authors.forename: Elisa
authors.initials: E
authors.lastname: Boscolo
authors.forename: Marianne
authors.initials: M
authors.lastname: Kambouchner
authors.forename: Aurélie
authors.initials: A
authors.lastname: Cazes
authors.forename: Olaf
authors.initials: O
authors.lastname: Mercier
authors.forename: Marc
authors.initials: M
authors.lastname: Humbert
authors.forename: Pascale
authors.initials: P
authors.lastname: Gaussem
authors.forename: Joyce
authors.initials: J
authors.lastname: Bischoff
authors.forename: Dominique
authors.initials: D
authors.lastname: Israël-Biet
mesh_terms: D042501:Angiogenic Proteins / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D002454:Cell Differentiation; D002455:Cell Division; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000096:biosynthesis / Q000235:genetics; D003094:Collagen; D003114:Colony-Forming Units Assay; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004338:Drug Combinations; D042783:Endothelial Cells / Q000473:pathology*; D005312:Fetal Blood / Q000166:cytology; D005347:Fibroblasts / Q000473:pathology*; D005355:Fibrosis; D020869:Gene Expression Profiling; D006412:Hematopoietic Stem Cells / Q000473:pathology*; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000473:pathology / Q000503:physiopathology*; D007797:Laminin; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008819:Mice, Nude; D018919:Neovascularization, Physiologic; D011509:Proteoglycans; D019718:Receptors, CXCR4 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*
chemical_list: D042501:Angiogenic Proteins; C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; C514936:CXCR4 protein, mouse; D054377:Chemokine CXCL12; D017077:Culture Media, Conditioned; D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; D019718:Receptors, CXCR4; C059485:matrigel; D003094:Collagen
keywords: CXCR4; ECFC; Fibrocytes; endothelial progenitor cells; pulmonary fibrosis
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