Τίτλος:
The hematopoietic chemokine CXCL12 promotes integration of human endothelial colony forming cell-derived cells into immature vessel networks
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Proangiogenic factors, vascular endothelial growth factor (VEGF), and fibroblast growth factor-2 (FGF-2) prime endothelial cells to respond to "hematopoietic" chemokines and cytokines by inducing/upregulating expression of the respective chemokine/cytokine receptors. Coculture of human endothelial colony forming cell (ECFC)-derived cells with human stromal cells in the presence of VEGF and FGF-2 for 14 days resulted in upregulation of the "hematopoietic" chemokine CXCL12 and its CXCR4 receptor by day 3 of coculture. Chronic exposure to the CXCR4 antagonist AMD3100 in this vasculo/angiogenesis assay significantly reduced vascular tubule formation, an observation recapitulated by delayed AMD3100 addition. While AMD3100 did not affect ECFC-derived cell proliferation, it did demonstrate a dual action. First, over the later stages of the 14-day cocultures, AMD3100 delayed tubule organization into maturing vessel networks, resulting in enhanced endothelial cell retraction and loss of complexity as defined by live cell imaging. Second, at earlier stages of cocultures, we observed that AMD3100 significantly inhibited the integration of exogenous ECFC-derived cells into established, but immature, vascular networks. Comparative proteome profiler array analyses of ECFC-derived cells treated with AMD3100 identified changes in expression of potential candidate molecules involved in adhesion and/or migration. Blocking antibodies to CD31, but not CD146 or CD166, reduced the ECFC-derived cell integration into these extant vascular networks. Thus, CXCL12 plays a key role not only in endothelial cell sensing and guidance, but also in promoting the integration of ECFC-derived cells into developing vascular networks. © Mary Ann Liebert, Inc. 2014.
Συγγραφείς:
Newey, S.E.
Tsaknakis, G.
Khoo, C.P.
Athanassopoulos, T.
Camicia, R.
Zhang, Y.
Grabowska, R.
Harris, A.L.
Roubelakis, M.G.
Watt, S.M.
Περιοδικό:
Stem Cells and Development
Εκδότης:
MARY ANN LIEBERT INC PUBL
Λέξεις-κλειδιά:
chemokine receptor CXCR4; fibroblast growth factor 2; plerixafor; stromal cell derived factor 1; vasculotropin; chemokine receptor CXCR4; CXCL12 protein, human; heterocyclic compound; stromal cell derived factor 1; vasculotropin A, angiogenesis; Article; blood vessel; cell labeling; cell proliferation; coculture; colony forming cell; controlled study; enzyme linked immunosorbent assay; hematopoiesis; human; human cell; long term exposure; mesenchymal stroma cell; pericyte; skin fibroblast; stroma cell; time lapse imaging; umbilical vein endothelial cell; vascular network; blood vessel; cell culture; cell motion; drug effects; endothelium cell; hematopoietic system; metabolism; physiology; procedures, Blood Vessels; Cell Movement; Cell Proliferation; Cells, Cultured; Chemokine CXCL12; Coculture Techniques; Endothelial Cells; Hematopoietic System; Heterocyclic Compounds; Humans; Receptors, CXCR4; Vascular Endothelial Growth Factor A
DOI:
10.1089/scd.2014.0005
