For the first time, a team of engineers and neuroscientists have demonstrated that human brain organoids implanted in mice have established functional connectivity to the animals’ cortex and responded to external sensory stimuli. The study, published in the journal Nature Communications, was led by Duygu Kuzum from the University of California San Diego Department of Electrical and Computer Engineering and involved researchers from Boston University, UC San Diego, and the Salk Institute.
Human cortical organoids are derived from human induced pluripotent stem cells and have recently emerged as a promising model for studying the development of the human brain and various neurological conditions. However, previous attempts to demonstrate functional connectivity and responsiveness to stimuli in implanted organoids have been unsuccessful due to limitations in recording technologies.
To overcome this challenge, the team developed a combination of transparent graphene microelectrode arrays and two-photon imaging, which allowed them to record and image neuronal activity in real time. When a visual stimulus was applied, the implanted organoids evoked electrophysiological responses that matched those of the surrounding cortex. The researchers also observed that mouse blood vessels grew into the organoids, providing necessary nutrients and oxygen.
The study represents a significant step forward in the use of organoids as models for brain development and disease, as well as their potential use as neural prosthetics to restore function to damaged brain regions. “This experimental setup opens up unprecedented opportunities for investigations of human neural network-level dysfunctions underlying developmental brain diseases,” said Kuzum.