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Human blood system in mice

In order to ensure their survival, tumours make full use of the body’s blood supply: they prompt the growth of blood vessels to supply the tumour. Scientists from the cooperative research area “Vascular Biology” at the Faculty of Medicine Mannheim of the University of Heidelberg and the German Cancer Research Centre have joined forces with colleagues from Freiburg and developed a method that can be used to create a complex human vascular system in mice.

The formation of new blood vessels, or angiogenesis, is essential for tumour growth and the lack of angiogenesis is the Achilles' heel of tumour growth as tumours depend on the supply of oxygen and nutrients for survival. Therefore, for some years now substances called angiogenesis inhibitors have been used in cancer treatment to suppress the process of formation of new blood vessels. In order to advance this new field of research, a team of researchers headed by Professor Hellmut Augustin has developed a method to create a complex human vascular system in mice, which stays functional even after several months.
Three-dimensional reconstruction of a vasculature (green) from human vascular wall cells in the mouse 10 days after the injection of spheroids. The picture was recorded with a confocal microscope. (Photo: Professor Hellmut Augustin, joint research area “V
Three-dimensional reconstruction of a vasculature (green) from human endothelial cells in the mouse 10 days after the injection of spheroids. The picture was recorded with a confocal microscope. (Photo: Professor Hellmut Augustin, cooperative research area “Vascular Biology” of the Faculty of Medicine Mannheim at the University of Heidelberg and the DKFZ)

Formation of a network of human blood vessels

The method is based on the observation that isolated cells of the vessel walls, known as endothelial cells, congregate spontaneously in cell cultures to form aggregates known as spheroids. “Individual endothelial cells floating in suspension are doomed to die – the cells are stabilised when they form spheroids,” said Hellmut Augustin. The scientists Abdullah Alajati and Anna Laib succeeded in injecting such spheroids (embedded in a gel matrix) under the skin of mice and to stimulate the formation of a network of human blood vessels using growth factors. ”The mice were genetically modified in such a way that their immune system was unable to reject the foreign cells. “The newly formed blood vessels exclusively consist of human endothelial cells,” explains Anna Laib, a young researcher at the DKFZ. “At the border of the matrix, the human endothelial cells establish contact with those of the mouse. That is how the transplanted human vasculature connects to the blood circulation of the mouse.
Three-dimensional analysis of the blood vessels formed shows that growth factors such as the fibroblast growth factor (FGF2) effectively promote the coating of the newly formed blood vessels (stained green) with smooth muscle cells (stained red). The pict
Three-dimensional analysis of the blood vessels formed shows that growth factors such as the fibroblast growth factor (FGF2) effectively promote the coating of the newly formed blood vessels (stained green) with smooth muscle cells (stained red). The picture was taken with a confocal microscope. (Photo: Professor Hellmut Augustin, cooperative research area “Vascular Biology” of the Faculty of Medicine Mannheim at the University of Heidelberg and the DKFZ)
The method provides experimental freedom and may deliver answers to various questions in vascular biology research. Scientists can genetically manipulate the endothelial cells before transplantation in order to investigate the formation of vascular networks. In addition, it is possible to test the effect of pharmacological substances; the Freiburg-based company ProQinase GmbH, which is involved in the study, is already conducting such experiments. "The method is even of potential interest in the production of artificial tissues," Hellmut Augustin says. "So far, one of the difficulties with the use of artificial replacement tissues has been to create a functioning vascular system that supplies enough oxygen and nutrients to the tissue constructs."

Literature: Abdullah Alajati, Anna M Laib, Holger Weber, Anja M Boos, Arne Bartol, Kristian Ikenberg, Thomas Korff, Hanswalter Zentgraf, Cynthia Obodozie, RalphGraeser, Sven Christian, Günter Finkenzeller, G Björn Stark, Mélanie Héroult & Hellmut G Augustin: Spheroid-based engineering of a human vasculature in mice. Nature Methods, April 2008, DOI: 10.1038/nmeth.1198



Source: DKFZ - 14.04.2008
Website address: https://www.gesundheitsindustrie-bw.de/en/article/news/human-blood-system-in-mice