Serious diabetic complications such as kidney failure, blindness or non-healing wounds are caused by a damage to blood vessels. Therefore, it is essential to understand the exact causes and correlations. However, animal experiments, for example with mice, are unsuitable because, comparable injuries of the blood vessels cannot be observed. Dr Reiner Wimmer and his team at IMBA are therefore working with organ-like systems (organoids) obtained from human cells.

They have succeeded in producing tiny human capillaries from induced pluripotent stem cells, which they supplied with a sugar-rich medium in combination with inflammatory messengers in the Petri dish. They were able to observe that the basement membrane surrounding and supporting the capillaries increased in size, which is also the case in diabetes patients. This leads to an inhibition of the supply of oxygen and nutrients to the vessels, which eventually leads to the death of the vessel.

In a next experiment, they tested some approved drugs in their diabetes vessel model, but they were unable to stop this development. However, the inhibition of a signalling pathway proved to be very promising. The signalling pathway proteins Notch3 and DLL4 were involved in the regulation of basement membrane thickness. Notch3 also showed this correlation in patients.

The in vitro results could offer completely new perspectives for future treatments of diabetes patients.

Original publication:
Reiner A. Wimmer, Alexandra Leopoldi, Martin Aichinger, Nikolaus Wick, Brigitte Hantusch, Maria Novatchkova, Jasmin Taubenschmid, Monika Hämmerle, Christopher Esk, Joshua A. Bagley, Dominik Lindenhofer, Guibin Chen, Manfred Boehm, Chukwuma A. Agu, Fengtang Yang, Beiyuan Fu, Johannes Zuber, Juergen A. Knoblich, Dontscho Kerjaschki & Josef M. Penninger (2019). Human blood vessel organoids as a model of diabetic vasculopathy. Nature,
doi.org/10.1038/s41586-018-0858-8

Source:
https://www.presseportal.de/pm/81715/4168101