An unprecedented opportunity exists to simulate human brain development and disease by dividing human pluripotent stem cells into tiny brainlike organoids. We developed a technique for transplanting human brain organoids into adult mouse brains in order to provide a vascularized and functional in vivo model of brain organoids. Organoid joins showed moderate neuronal separation and development, gliogenesis, combination of microglia and development of axons to various areas of the host cerebrum. Two-photon in vivo imaging revealed the grafts' functional neuronal networks and blood vessels. Finally, optogenetics and in vivo extracellular recording revealed intragraft neuronal activity and suggested functional synaptic connectivity between the host and the graft. It's possible that disease modeling under physiological conditions will be made easier by combining human neural organoids with an in vivo physiological environment in the animal brain.
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