Human Brain Cells Form Neural Networks in Mice, With Potential Applications in Drug Development

A study has found that mice implanted with human brain cells form neural networks, potentially enabling their use in drug development.

According to the Korea Biotechnology Industry Organization’s Bioeconomy Research Center, a study finding that organoids grown in the laboratory formed neural networks with the brains of mice missing key brain regions was published on the 16th (local time) in the international journal Nature.

The findings are considered to offer a new way to test treatments for neurodevelopmental disorders.

Access to human brain tissue has long been difficult, limiting research into development and function. Human stem cell-derived neural models are beginning to address this challenge, the researchers said.

Neuroscientists have struggled for decades with the inability to study living human brain tissue. “Human brain organoids,” made by growing human stem cells in a dish, have served as a window into early neural development, but they generally lack blood vessels and the bodily environment needed to exchange signals.

Using a genetic strategy, the researchers removed glutamatergic neurons from the neocortex and hippocampus of mice. They then implanted human stem cell-derived cortical organoids into the cortical cavity when the mice were at a stage corresponding to the neonatal period, creating “xenocortical mice.”

As a result, the transplanted tissue grew successfully, occupying most of the cortical volume and generating various human cortical cell types.

To determine whether the transplanted tissue could mimic human disease, the research team exposed the mice to hypoxic conditions associated with cerebral palsy in premature infants. Only the mice that received human tissue showed deficits in motor coordination similar to those seen in people with cerebral palsy.

This suggests that the transplanted tissue could be used to test treatments for cerebral palsy.

Sergiu Pasca, a neuroscientist at Stanford University and co-author of the study, said these “hybrid animals” offer an unprecedented way to study disorders involving abnormal brain development, such as cerebral palsy, and test drugs.

The researchers said they expect xenocortical technology to be useful for obtaining circuit- and behavior-level data using human neurons for neurodevelopmental research, disease modeling and therapeutic development.