Spheroid-based engineering of a human vasculature in mice.
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.
Alajati
Abdullah
A
Joint Research Division Vascular Biology of the Medical Faculty Mannheim (CBTM), University of Heidelberg, Ludolph-Krehl-Str. 11-14, D-68167 Mannheim, Germany.
Laib
Anna M
AM
Weber
Holger
H
Boos
Anja M
AM
Bartol
Arne
A
Ikenberg
Kristian
K
Korff
Thomas
T
Zentgraf
Hanswalter
H
Obodozie
Cynthia
C
Graeser
Ralph
R
Christian
Sven
S
Finkenzeller
Günter
G
Stark
G Björn
GB
Héroult
Mélanie
M
Augustin
Hellmut G
HG
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
D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2