Neuronal implants in rats pave the way for treating brain injuries

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

“Neural tissues have the potential to rebuild areas of the injured brain,” said Isaac Chen, who led the study at the University of Pennsylvania, adding that the implants helped rats recognize light patterns in the visual cortex. “It’s a very solid first step.”

The Penn team converted human stem cells into brain organoids, neural structures a few millimeters in diameter with many features of real brains that have become one of the hottest research areas in neuroscience.

The organoids were transplanted into the brains of rats whose own visual cortex – the area that processes visual information from the eyes – had been partially removed. Within three months, the human organoids successfully integrated into the rat’s brain, sharing its blood supply, increasing in size and number, and forming connections with the host’s neurons. The researchers suppressed the animals’ immune systems to prevent rejection of the human tissue.

Details of the experiment were published on Thursday in Cell Stem Cell magazine. The next phases of the Penn research program will examine the ability of organoids to grow in areas of the adult brain other than the visual cortex.

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

A human organoid that fluoresces green in a rat brain

Green fluorescence shows an implanted human organoid growing in a rat brain © Dennis Jgamadze UPenn

The fluorescence tracing techniques used in the experiment revealed continuous neuronal connections from the rat retina 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 large number of neurons within the organoid responded to specific directions of light, giving us evidence that these organoid neurons were not only able to integrate into the visual system, but also very specific functions of the visual cortex,” Chen said.

The researchers were surprised by the rapid neural integration in the adult brain, which is encouraging for potential medical procedures such as treating damage from stroke or severe head injuries. In previous studies, rapid and successful integration occurred only when human brain tissue was implanted into newborn rodents, whose developing brain provides a biochemical environment more conducive to neuronal growth.

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

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

However, this process would be time-consuming and expensive for healthcare providers.

“A more sensible approach might be patient-adapted tissues — where there is a library of stem cells and off-the-shelf tissues that match a patient’s immune signature, eliminating the need for immunosuppressive drugs,” Chen said. Neuronal implants in rats pave the way for treating brain injuries

Adam Bradshaw

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