A small amount of human brain tissue grown in the lab has been successfully transferred into the nervous systems of rats.
The 3D organoids were developed from stem cells to resemble a simplified model of the human cortex, connected and integrated with the surrounding tissue in each rat's cortex to form a functional part of the rodents' own brain.
The limitations of dish-grown organoids have been overcome by a team of researchers led by Sergiu Paca.
Paca said that most of the work that his lab has been doing has been motivated by trying to understand psychiatric disorders at the biological level.
Many of the psychiatric conditions are anchored in unique features of the human brain. Progress in understanding the biology of these conditions has been hampered by the fact that the human brain is not very accessible.
Scientists were able to grow brain cells from stem cells. Stem cells from adult humans were reverse engineered to return them to the blank state they were in before they became specialized cells.
Stem cells were guided to develop into brain cells, which were then grown into organoids. The wrinkled outer cortex is one of the key parts of the brain that could be studied.
cortical organoids have limitations They don't complete maturation because they aren't connected to living systems.
A brain organoid in a dish can't show the behavioral consequences of defects. The ability to identify the characteristics of the disorders is hampered by the fact that they are defined by behavior.
Scientists have tried to overcome hurdles by implanting human brain organoids into rats. The organoid couldn't form a strong connection with an adult rat brain because of the mismatch.
Paca and his colleagues tried to use human brain tissue to grow the brains of rats who have not yet developed their own brains.
Human cortical organoids were cultured in a dish and then transferred into the somatosensory cortex of rats just a few days old. The rats were left to grow into adults for 140 days.
Scientists looked at the rats. The organoids were genetically engineered to respond to blue light. The rats were being trained to lick a spout and this stimulation was done on the human brain. The rats licked the organoids when the blue light shone on them.
It was shown that the organoid was part of the rat brain and could help drive reward-seeking behavior.
When the scientist pushed the rats' whiskers, another group of neurons in the organoids showed activity.
Some of the organoids were made using brain cells from three humans with a genetic disease. Early death is usually the result of Timothy syndrome.
Rats were euthanized and their brains were removed, allowing researchers to observe the integration of organoids on a cellular level. They found that the organoid neurons grew larger than the native rat neurons.
Compared to control groups, the rats with Timothy syndrome had less elaborate shapes of the neurons. A brain organoid could not have been found in a dish.
The team believes that the platform has the potential to be a powerful tool for understanding brain development and disease.
The authors write in their paper that the platform represents a powerful resource to complement studies of human brain development.
This platform will allow us to uncover new circuit-level phenotypes in patient-derived cells that have been elusive and to test novel therapeutic strategies.
The research was published in a journal.
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