title: Density of human bone marrow stromal cells regulates commitment to vascular lineages.
abstract: Mechanisms underlying the vascular differentiation of human bone marrow stromal cells (HBMSCs) and their contribution to neovascularisation are poorly understood. We report the essential role of cell density-induced signals in directing HBMSCs along endothelial or smooth muscle lineages. Plating HBMSCs at high density rapidly induced Notch signaling, which initiated HBMSC commitment to a vascular progenitor cell population expressing markers for both vascular lineages. Notch also induced VEGF-A, which inhibited vascular smooth muscle commitment while consolidating differentiation to endothelial cells with cobblestone morphology and characteristic endothelial markers and functions. These mechanisms can be exploited therapeutically to regulate HBMSCs during neovascularisation.
authors.affiliation: Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, UK.
authors.forename: Jemima L
authors.initials: JL
authors.lastname: Whyte
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Ball
authors.forename: C Adrian
authors.initials: CA
authors.lastname: Shuttleworth
authors.forename: Keith
authors.initials: K
authors.lastname: Brennan
authors.forename: Cay M
authors.initials: CM
authors.lastname: Kielty
mesh_terms: D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism; D002452:Cell Count; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000378:metabolism; D017154:Stromal Cells / Q000166:cytology* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D055815:Young Adult
chemical_list: D042461:Vascular Endothelial Growth Factor A