Stanford scientists grow human tissue through most of a mouse cortex

Stanford University researchers have replaced much of a mouse’s brain with laboratory-grown human tissue, overcoming the lack of space that has long limited the transplantation of brain organoids, ERR reported. The method could allow scientists to study human brain development and diseases in a living, moving organism.

Because living human brain tissue is difficult to obtain, researchers have spent the past decade growing three-dimensional brain models, known as organoids, from patients’ stem cells. These “mini-brains” are kept alive in specially adapted containers, but their development remains incomplete in laboratory conditions.

Artificial environments do not provide natural blood circulation or sensory signals. The cell masses also cannot influence the behaviour of a living organism while in a laboratory container. To overcome these limitations, scientists have previously transplanted small organoids into the brains of rodents.

However, the skull of a developing host can hold only a limited amount of additional material. At the same time, the mouse’s rapidly developing neural network pushes aside the more slowly growing human tissue, preventing the human cells from forming sufficiently extensive connections in the rodent brain.

Creating room for human cells

The Stanford researchers used a genetic switch to stop the development of the mouse’s cerebral cortex and hippocampus. These regions are involved in perception and complex movement in mammals. This created a large cavity inside the mouse’s skull, leaving higher brain centres, including speech and movement centres, largely without cells.

The scientists transplanted four human cortical organoids at an early stage of development into the empty space. In the larger environment, the human tissue grew as expected and vigorously.

Within a few months, the transplanted tissue filled nearly 90 percent of the missing volume of the mouse’s cerebral cortex. The human cells did not remain anatomically separate, but sent extensions into the animal’s remaining brain regions. Some nerve fibres reached the mouse’s spinal cord in the neck region.

According to Sergiu Pașca, who led the research team, the animal developed a neural network with synchronised electrical activity. In other words, the human tissue clearly responded to movements in the mouse’s facial region. This showed the researchers that the transplanted cells had successfully integrated with the host’s nervous system.

The more spacious environment produced another biological advance. Rare deep-layer neurons began to develop in the transplanted tissue. These cells resemble von Economo neurons found in large mammals, but do not survive in ordinary laboratory containers.

The development of these rare cells could create new opportunities for studying psychiatric disorders. Many problems involving human social perception are linked to the function of these brain cells, which researchers can now study in a living organism.