Neural implants in rats pave way to treat brain injuries

US researchers have shown that brain tissue implanted into adult rats can integrate with the animals’ own neurons, raising the prospect that cerebral transplants will be able to repair damage from head injury or disease.

“Neural tissues have the potential to rebuild areas of the injured brain,” said Isaac Chen, leader of the study at the University of Pennsylvania, adding that the implants helped rats recognise light patterns in the visual cortex. “This is a very solid first step.”

The Penn team converted human stem cells into brain organoids, neural structures a few millimetres across with many of the features of real brains, which have become one of the hottest research fields in neuroscience.

The organoids were grafted into the brains of rats whose own visual cortex — the area processing visual information from the eyes — had been partially removed. Within three months the human organoids successfully integrated into the rat brain, sharing its blood supply, growing in size and number and forming connections with the host neurons. The researchers had suppressed the animals’ immune system to prevent rejection of the human tissues.

Details of the experiment were published on Thursday in the journal Cell Stem Cell. The next stages in the Penn research programme will investigate the capacity for organoids to grow in other areas of the adult brain besides the visual cortex.

“We also want to understand the factors that guide the integration process, so that we can adjust the composition of the organoid and aspects of the host brain to make them integrate as well as possible,” said Chen.

Fluorescent tracing techniques used in the experiment showed continuous neuronal connections from the rats’ retinas to the organoid. Then miniature probes measured the activity of individual human neurons when the animals were exposed to flashing lights and patterns of alternating black and white bars.

“We saw that a good number of neurons within the organoid responded to specific orientations of light, which gives us evidence that these organoid neurons were able not just to integrate with the visual system, but they were able to adopt very specific functions of the visual cortex,” Chen said.

The researchers were surprised by the swift neural integration inside the adult brain, which is encouraging for possible medical procedures such as treating the damage caused by strokes or serious head injuries. In previous studies fast and successful integration occurred only when human brain tissue was implanted into newborn rodents, whose developing brains provide a biochemical environment more conducive to neuronal growth.

“Our work shows that the adult brain is still [adaptable] enough to integrate new tissue,” said Chen. “One day we will be able to exploit that to develop procedures for patients.”

One approach would be for clinicians to take skin cells from a brain-injured patient, turn them into stem cells with a biochemical cocktail and then guide their development over a few weeks into a brain organoid. This would then be implanted into the injured or damaged brain area.

But that process would be time-intensive and expensive for healthcare providers.

“A more reasonable approach could be patient-matched tissue — where there is a library of stem cells and off-the-shelf tissue that match the immune signature of a patient so that immunosuppressant drugs are not needed,” said Chen.