Cardiovascular research: Generation of endothelial cells from stem cells

Endothelial cells line the inside of blood vessels and fulfil essential functions such as the regulation of blood pressure and blood clotting. They are also involved in the development of cardiovascular diseases. Human endothelial cells are required for research into these diseases outside the body. "Human induced pluripotent stem cells (hiPSCs) are a promising approach for this. Since they are not yet committed to a specific tissue type, they have the potential to differentiate into many different cell types - including endothelial cells," explains Prof. Bernd K. Fleischmann, Director of the Institute of Physiology I at the University Hospital Bonn. 

Various differentiation strategies for hiPSCs into endothelial cells have been developed in the past. One of the latest methods is based on the activation of the transcription factor "ETS variant transcription factor 2" (ETV2), which has been identified as a key factor in the conversion of stem cells into endothelial cells. Researchers at Harvard Medical School and the University Hospital Bonn developed a special hiPSC line called "PGP1 ETV2 iso2", which can specifically activate ETV2 by adding doxycycline. 

The team led by Dr Sarah Rieck and Prof Volker Busskamp improved the existing protocol for differentiating these cells. The optimised ETV2 protocol offers a faster and more cost-effective way to generate endothelial cells compared to conventional methods based on growth factors. 

The results show that the new ETV2 protocol is highly reproducible and can be easily transferred to other hiPSC lines. The generated cells have characteristic proteins and functional properties of endothelial cells and are also stable over longer periods of time. In addition, the protocol enables the generation of endothelial cells with specific arterial or venous characteristics. 

The researchers see great potential for the use of the generated endothelial cells in cardiovascular disease research. For example, they can be used to model diseases in the cell culture dish. They also offer opportunities in organoid research to develop organoids with a vascular system. 

These research questions are being investigated in the Transregional Collaborative Research Centre 259 'Aortic Diseases', in which Dr Rieck and Prof. Fleischmann are involved. The endothelial cells could also become relevant for future clinical applications. 

MEDICA-tradefair.com; Source: Bonn University Hospital