title: Spheroid-based engineering of a human vasculature in mice.
abstract: The complexity of the angiogenic cascade limits cellular approaches to studying angiogenic endothelial cells (ECs). In turn, in vivo assays do not allow the analysis of the distinct cellular behavior of ECs during angiogenesis. Here we show that ECs can be grafted as spheroids into a matrix to give rise to a complex three-dimensional network of human neovessels in mice. The grafted vasculature matures and is connected to the mouse circulation. The assay is highly versatile and facilitates numerous applications including studies of the effects of different cytokines on angiogenesis. Modifications make it possible to study human lymphangiogenic processes in vivo. EC spheroids can also be coimplanted with other cell types for tissue engineering purposes.
authors.affiliation: Joint Research Division Vascular Biology of the Medical Faculty Mannheim (CBTM), University of Heidelberg, Ludolph-Krehl-Str. 11-14, D-68167 Mannheim, Germany.
authors.forename: Abdullah
authors.initials: A
authors.lastname: Alajati
authors.forename: Anna M
authors.initials: AM
authors.lastname: Laib
authors.forename: Holger
authors.initials: H
authors.lastname: Weber
authors.forename: Anja M
authors.initials: AM
authors.lastname: Boos
authors.forename: Arne
authors.initials: A
authors.lastname: Bartol
authors.forename: Kristian
authors.initials: K
authors.lastname: Ikenberg
authors.forename: Thomas
authors.initials: T
authors.lastname: Korff
authors.forename: Hanswalter
authors.initials: H
authors.lastname: Zentgraf
authors.forename: Cynthia
authors.initials: C
authors.lastname: Obodozie
authors.forename: Ralph
authors.initials: R
authors.lastname: Graeser
authors.forename: Sven
authors.initials: S
authors.lastname: Christian
authors.forename: Günter
authors.initials: G
authors.lastname: Finkenzeller
authors.forename: G Björn
authors.initials: GB
authors.lastname: Stark
authors.forename: Mélanie
authors.initials: M
authors.lastname: Héroult
authors.forename: Hellmut G
authors.initials: HG
authors.lastname: Augustin
mesh_terms: D000818:Animals; D002450:Cell Communication; D018929:Cell Culture Techniques / Q000379:methods*; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D006801:Humans; D051379:Mice; D018919:Neovascularization, Physiologic / Q000502:physiology*; D018874:Spheroids, Cellular / Q000166:cytology*; D023822:Tissue Engineering; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology
chemical_list: D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2