Transplanted Human Cortical Organoids

Transplanted Human Cortical Organoids

One of the largest hurdles in the advancement of medicinal sciences is its applicability to heal or cure. Numerous strides have been made in order to close this gap by revolutionizing the mouse animal model. The ability of the animal to contain any human-derived cells or tissue used for therapeutic drug efficacy, toxicity, or bioavailability testing is essential in fine-tuning drug development.

An early model was synthesized by Yecuris using live donor-derived human hepatocytes engrafted into the mouse’s liver and allowed to repopulate with an 85-95% repopulation rate. While the liver is important in exploring metabolic and hepatic diseases, the ability to explore psychiatric disorders such as schizophrenia, or post-traumatic stress disorders has the potential to significantly impact mental health.

Recently, advancements in neuroscience have been made by scientists at Stanford University. The use of neural organoids is a promising platform used to study psychiatric disease onset and development; however, they lack the neuronal connectivity found only in living systems. The lack of neuronal connectivity makes integration with other neuronal circuits that drive disease onset and behavior impossible. The scientists transplanted human stem cell-derived cortical organoids into the somatosensory cortex of newborn athymic rats. The transplanted cells then developed into mature cell types that integrated into the sensory and motivation-related neuronal circuits.

While the cells showed integration, the pivotal moment of the study demonstrated anatomical and functional tracings revealing that the transplanted organoids were receiving thalamocortical and corticocortical electrical inputs, which produced sensory responses within the human organoids. Additionally, the cortical organoid axons extended throughout the rat brain, and optogenetic activation was shown to drive reward-seeking behavior.

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