TY - JOUR
T1 - Cooperation between human fibrocytes and endothelial colony-forming cells increases angiogenesis via the CXCR4 pathway
AU - Smadja, David M.
AU - Dorfmüller, Peter
AU - Guerin, Coralie L.
AU - Bieche, Ivan
AU - Badoual, Cécile
AU - Boscolo, Elisa
AU - Kambouchner, Marianne
AU - Cazes, Aurélie
AU - Mercier, Olaf
AU - Humbert, Marc
AU - Gaussem, Pascale
AU - Bischoff, Joyce
AU - Israël-Biet, Dominique
N1 - Publisher Copyright:
© Schattauer 2014.
PY - 2014/1/1
Y1 - 2014/1/1
N2 - 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 cordblood- 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.
AB - 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 cordblood- 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.
KW - CXCR4
KW - ECFC
KW - Endothelial progenitor cells
KW - Fibrocytes
KW - Pulmonary fibrosis
UR - http://www.scopus.com/inward/record.url?scp=84908507260&partnerID=8YFLogxK
U2 - 10.1160/TH13-08-0711
DO - 10.1160/TH13-08-0711
M3 - Article
C2 - 25103869
AN - SCOPUS:84908507260
SN - 0340-6245
VL - 112
SP - 1002
EP - 1013
JO - Thrombosis and Haemostasis
JF - Thrombosis and Haemostasis
IS - 5
ER -