Abstract

From Brain Organoids to Animal Chimeras: Novel Platforms for Studying Human Brain Development and Disease

Abed Mansour, EMBO Fellow, The Salk Institute

Due to the immense complexity of the human brain, the study of its development, function, and dysfunction during health and disease has proven to be challenging. The advent of patient-derived human induced pluripotent stem cells, and subsequently their self-organization into three-dimensional brain organoids, which mimics the complexity of the brain's architecture and function, offers an unprecedented opportunity to model human brain development and disease in new ways. However, there is still a pressing need to develop new technologies that recapitulate the long-term developmental trajectories and the complex in vivo cellular environment of the brain. To address this need, we have developed a human brain organoid-based approach to generate a chimeric human/animal brain system that facilitates long-term anatomical integration, differentiation, and vascularization in vivo. We also demonstrated the development of functional neuronal networks within the brain organoid and synaptic-cross interaction between the organoid axonal projections and the host brain. This approach set the stage for investigating human brain development and mental disorders in vivo, and run therapeutic studies under physiological conditions.