Scientists implanted human neurons within the brains of new child mice: the controversial examine

A Stanford University research team implanted human brain organoids into the brains of mice, which integrated and connected.

In human brain tissue lighter green in mouse brain. Credit: Stanford University.

Organoids composed of human neurons were implanted in the brains of newborn mice, where they integrated and developed neural connections. The controversial experiment was carried out with the aim of demonstrating the feasibility of studying neurological and psychiatric diseases. The research authors point out that organoids – also known as ‘mini-brains’ – are valid models for studying certain brain functions, however, in the absence of blood flow and signals derived from the senses (neural connections), effectiveness and development are severely compromised. limited. . . For this reason, they are considered to be of little use for studying conditions related to circuit formation, such as autism and schizophrenia. To overcome the problem, the scientists thought of implanting organoids in rodents, thus creating a living hybrid organism (a mouse-human chimera) in which it is possible to better verify the brain processes linked to mental pathologies.

Leading the experiment was an American research team led by scientists from the Department of Psychiatry and Behavioral Sciences at the prestigious Stanford University, who worked closely with colleagues from the Departments of Bioengineering and Neurosurgery and the Wu Tsai Institute of Neuroscience and Bio-X. The researchers, coordinated by Professor Sergiu Pasca, created the organoids measuring a few millimeters from induced pluripotent stem cells obtained from human skin cells, after specific treatment with a biochemical cocktail to reprogram them in an immature state and transform them into neurons. in the cortex (the outermost layer of the brain). Cells grown in a dish gave rise to mini-brains that were implanted into two- or three-day-old mice, genetically modified to lack an immune system and thus avoid the risk of rejection of human brain tissue.

After implantation, brain cells from mice migrated to human tissues, formed blood vessels, and initiated tissue nutrition, while human neurons formed connections with rodent brain structures, including the thalamus, which is the part responsible for transmitting information. sensory to the cortex. Specifically, cortical organoids were implanted in the animals’ primary somatosensory cortex, a part of the brain involved in processing sensations, as specified by the study authors. “This connection may have provided the necessary signaling for optimal maturation and integration of human neurons,” Professor Pasca said in a press release.

To verify the real connection between the human organoid and the mouse brain, the scientists infected the organoids with a viral marker, which spreads between brain cells and highlights functional connections. The developing organoids grew considerably and occupied up to a third of the rat’s cerebral hemisphere after 6 months. The connections between the two entities were tested through various experiments; for example, by stimulating rodent whiskers, an operation that caused the electrical activation of human neurons. In another phase of the study, optogenetics was also tested. Simply put, using blue laser light directed at organoids – with fiber optics implanted in the skull – the scientists were able to alter the rodents’ behavior, causing them to fetch water from a drinking trough “on command”. , thanks to light stimulation.

Some of the implanted organoids were created from stem cells obtained from patients with a genetic condition called Timothy syndrome, which is associated with autism and epilepsy. Once integrated, these organoids generated a specific structure, which allowed the researchers to highlight differences with implants from healthy cells. “This is the most advanced human brain circuit ever built from human skin cells and a demonstration that implanted human neurons can influence an animal’s behavior,” said Professor Pasca. “Our platform provides, for the first time, behavioral readouts for human cells and we hope to accelerate our understanding of complex psychiatric conditions,” he concluded.

Scientists are aware that such experiments have serious ethical implications that need to be thoroughly investigated, including the risk that mice with human brain tissue could develop more human thoughts and consciousness due to these implants, as the one pointed out to the Tara Spiers science center. – Jones, professor at the UK Dementia Research Institute at the University of Edinburgh. Details of the research “Maturation and integration of transplanted human cortical organoid circuits” were published in the scientific journal Nature.

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