Modelling the neurovascular niche in a long-lived human brain organoid system

Between 2019 and 2023, over 915,000 rodents were used internationally in studies on brain trauma and development; in Germany alone, 770 animal testing projects were approved in 2021 under the heading ‘Neuro’. This high number of animal experiments, particularly those involving rodents, not only raises ethical questions but is also scientifically controversial due to the significant differences between rodent and human brains in terms of complexity and physiological properties. Against this backdrop, the proposed project aims to develop a long-lived human model system that replicates the neurovascular niche by integrating endothelial progenitor cells into novel neural organoid systems. These organoid systems are based on human stem cells and are intended to enable a better understanding of brain development, as well as the mechanisms of brain trauma and their treatment, without relying on animal testing.

The neurovascular niche plays a crucial role in the survival and self-renewal of stem cells in the brain. However, previous organoid models have been unable to adequately replicate this niche, which has limited the lifespan and functionality of the organoids. The targeted integration of endothelial cells into the organoid tissue aims to create an environment that ensures the long-term survival of the stem cells and, consequently, of the organoids. This approach promises to overcome the limitations of current models and provide a system that realistically replicates the complex interaction between neural stem cells and vascular cells in the human brain. The project’s research involves the development of a modified Lancaster model for neural organoid systems, in which endothelial progenitor cells are integrated as early as the formation phase. This integration enables the formation of vessel-like structures and the recreation of the neurovascular niche, which has already led to a significantly prolonged survival of the organoids in preliminary experiments. The addition of specific extracellular substances is intended to further promote and optimise the formation of this niche.

The project spans both basic research and application-oriented fields such as drug development and regenerative medicine. It offers the potential to deepen our understanding of brain development and the mechanisms underlying brain trauma, and to develop new therapeutic approaches. In the long term, this model system could help to significantly reduce the reliance on animal testing in neurological research and enable personalised therapeutic approaches by generating organoids from patient stem cells. In summary, the project represents an innovative approach to overcoming the limitations of existing models and creating a human organoid model that realistically replicates the neurovascular niche and associated processes in the brain. This could represent a significant advance in the research and treatment of brain diseases, as well as in the reduction of animal testing.