title: Mechanical strain regulates endothelial cell patterning in vitro.
abstract: Blood vessels of the vertebrate circulatory system typically exhibit tissue-specific patterning. However, the cues that guide the development of these patterns remain unclear. We investigated the effect of cyclic uniaxial strain on vascular endothelial cell dynamics and sprout formation in vitro in two-dimensional (2D) and three-dimensional (3D) culture systems under the influence of growth factors. Cells preferentially aligned and moved in the direction perpendicular to the major strain axis in monolayer culture, and mechanical strain also regulated the spatial location of cell proliferation in 2D cell culture. Cells in 3D cell culture could be induced to form sprouts by exposure to appropriate growth factor combinations (vascular endothelial growth factor and hepatocyte growth factor), and the strain direction regulated the directionality of this process. Moreover, cyclic uniaxial strain inhibited branching of the structures formed by endothelial cells and increased their thickness. Taken together, these data support the importance of external mechanical stimulation in the regulation of endothelial cell migration, proliferation, and differentiation into primitive vessels.
authors.affiliation: Division of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts, USA. tmatsu@dent.osaka-u.ac.jp
authors.forename: Takuya
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Yu Ching
authors.initials: YC
authors.lastname: Yung
authors.forename: Claudia
authors.initials: C
authors.lastname: Fischbach
authors.forename: Hyun Joon
authors.initials: HJ
authors.lastname: Kong
authors.forename: Ryusuke
authors.initials: R
authors.lastname: Nakaoka
authors.forename: David J
authors.initials: DJ
authors.lastname: Mooney
mesh_terms: D019521:Body Patterning / Q000502:physiology; D018929:Cell Culture Techniques / Q000295:instrumentation; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology* / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology* / Q000502:physiology; D006801:Humans; D013314:Stress, Mechanical; D014471:Umbilical Veins / Q000166:cytology / Q000502:physiology