Human brain organoids partially replace mouse cortex in new study
Stanford researchers engineered mice lacking most of their cerebral cortex and implanted human cortical organoids, which integrated and restored limited brain functions.
A team at Stanford University genetically eliminated a large portion of the mouse cerebral cortex and implanted human cortical organoids into the vacant region. The mice, bred without a functional cortex, survived after intensive nursing and high-calorie feeding, and more than 85% of the implanted organoids successfully integrated, accounting for about 92% of the cells in the resulting tissue.
The human cells differentiated into the major neuronal types found in cortex and extended long-range projections, some reaching the spinal cord. Electrophysiological recordings showed synchronized firing, indicating some functional connectivity. However, the grafted tissue lacked the layered architecture typical of a normal cortex, suggesting incomplete structural organization.
Behavioral testing revealed that mice with the humanized cortex displayed activity patterns distinct from both normal mice and cortex-deficient mice, occupying an intermediate position in weight and motor coordination measures. In a simple maze, these mice performed above chance but below normal levels, while on associative memory tasks they performed no better than cortex-less controls.
The researchers note that further anatomical and functional characterization is needed before the model can be deemed useful for studying complex neurodegenerative diseases. Nonetheless, the study demonstrates that human cortical cells can survive, mature, and form rudimentary networks in a mouse brain lacking its own cortex.