In Vivo Interrogation of Human Organoids Implanted in Mice Using Transparent Microgrids

Recent advances in pluripotent stem cell technology have enabled development of cerebral organoids from human induced pluripotent stem cells. The self-assembled, 3D structure of cerebral organoids resemble early developmental stages of the human brain. Transplantation of human cerebral organoids into the mouse brain have been performed to provide natural brain microenvironment crucial for maturation of long-term viability. However, chronic monitoring of transplanted organoids is challenging due to limitations of existing technologies. Here, we present optically transparent graphene microgrids as a functional two-photon imaging windows to enable multimodal longitudinal monitoring and interrogation of neuronal activity in the organoids and the surrounding host neuronal circuits. We envision that this technology can enable comprehensive experiments for modeling diseases, screening various treatment strategies, and as a replacement therapy for damaged brain regions.