Making an Alzheimer brain in a culture dish
Modelling tau pathology in human neuron/astrocyte co-cultures
This project aims for a technological tour-de-force: Induce Alzheimer pathology in 3D (co-)cultures of human stem-cell-derived neurons and astrocytes and 3D imaging in very small culture wells that can be used for drug screening. This project is made possible by the unique expertise of the VUmc in human stem-cell derived brain cultures and cell models for diseases of the brain combined with the expertise of OcellO in automated 3D microscopy.
Due to the aging population, dementia is a growing social-economic problem. However, up to now, animal studies have not yet provided any candidate drug that works in clinical trials. It seems that animal models do not adequately reflect the human brain situation. This underlines the need for better human models to develop an effective drug.
The current models in the field, including their own advanced 3D human model, largely take a neuron-centered view and ignore the role of astrocytes. Therefore, it is still largely unknown which effects Alzheimer exerts on human astrcytes and how astrocytes contribute to the disease. The advanced model they aim to develop incorporates both astrocytes and neurons in 3D, reflecting the situation in the human brain. When implemented in the OcellO platform this would present a superior model for drug screening.
The main deliverables of their project are: 2D and 3D culture models for Alzheimer in human astrocytes in monoculture and in co-culture with neurons. These can be implemented in research labs as well as for drug screening. Potentially the model reduces the use of experimental animals and speeds up drug discovery for Alzheimer.