E-Organoids: Functional Brain Organoids Co-grafted with Transparent Microthreads

多能干细胞技术的最新进展使大脑干细胞的产生成为可能

Recent advances in pluripotent stem cell technology have enabled generation of cerebral organoids from induced pluripotent stem cells derived from human peripheral tissues. Cerebral organoids are formed by self-assembled, 3D aggregates generated from stem cells with different cell types and layers mimic the embryonic human brain. Cerebral organoids open up unprecedented opportunities for studying brain development, investigation of neuronal network dysfunctions underlying human brain diseases, and providing an experimental system for drug testing and discovery. In vivo transplantation of cerebral organoids offers a transformative approach for future applications of transplantable regenerative medicine. Although tremendous breakthroughs have been made in organoid research in the recent years, two key challenges fundamentally limit their utility and further development towards a complete model system for investigation of human brain development and disorders. The first challenge is lack of a chronic functional interface for precise monitoring cellular and network-level activity of the organoids with high precision and the second challenge is lack of the natural brain microenvironment and vasculature impeding maturation of neurons and causing cell death at the organoid core. This project will overcome these challenges by creating E-Organoids with a seamless functional interface that will monitor activity of individual neurons and cell populations as well as supply oxygen and nutrients for healthy maturation, in vitro and in vivo. The proposed E- Organoids will create a complete platform combining in vivo electrophysiology and 2-photon microscopy for robust and quantitative in vivo functional evaluation of neuronal activity of human cortical organoids at the cellular and network level. In the future, this technology could allow systematic investigation of effects of new drugs on development and organization of human neuronal networks during development.