Nature Methods
- 5, 439 - 445 (2008)
Published online: 6 April 2008; | doi:10.1038/nmeth.1198
Spheroid-based engineering of a human vasculature in miceAbdullah Alajati1, 2, 3, 6, 7, Anna M Laib1, 7, Holger Weber2, 6, 7, Anja M Boos1, 2, Arne Bartol1, Kristian Ikenberg2, Thomas Korff2, 6, Hanswalter Zentgraf4, Cynthia Obodozie2, 6, Ralph Graeser5, Sven Christian1, 2, Günter Finkenzeller3, G Björn Stark3, Mélanie Héroult1, 2 & Hellmut G Augustin1, 21
Joint Research Division Vascular Biology of the Medical Faculty Mannheim (CBTM), University of Heidelberg, Ludolph-Krehl-Str. 11-14, D-68167 Mannheim, Germany, and the German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, D-69120 Heidelberg, Germany. 2
Department of Vascular Biology and Angiogenesis Research, Tumor Biology Center, Breisacher Str. 117, D-79108 Freiburg, Germany. 3
Department of Plastic and Hand Surgery, University of Freiburg Medical Center, Hugstetter Str. 55, D-79106 Freiburg, Germany. 4
Electron Microscopy Group, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany. 5
ProQinase GmbH, Breisacher Str. 117, D-79108 Freiburg, Germany. 6
Present addresses: Friedrich-Miescher Institute, Maulbeerstrasse 66, CH-4058 Basel, Switzerland (A.A.); ProQinase GmbH, Breisacher Str. 117, D-79108 Freiburg, Germany (H.W., C.O.); Department of Physiology, University of Heidelberg, Im Neuenheimer Feld 581, D-69120 Heidelberg, Germany (T.K.). 7
These authors contributed equally to this study.
Correspondence should be addressed to Hellmut G Augustin augustin@angiogenese.de 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.
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