2022-10-24| R&D

Scientists Make Rat-Human Hybrid Brain for Neuropsychiatric Research Purposes

by GeneOnline
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Self-organizing neural organoids represent a promising in vitro platform to model human development and diseases. A recent paper published in Nature showed that by transplanting miniature human-brain-like structures into rats’ brains, scientists could successfully send signals and observe whisker stimulation and deflection according to environmental changes in the surroundings. These findings suggest that neurons grown from human stem cells can interact with the nerve cells of living rodents and may be useful for future experiments for therapeutic approaches to human brain diseases.

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Transplanting Human-brain-like Structures into Newborn Rats

A team of researchers at Stanford University used human stem cells to grow cortical organoids, which they injected and transplanted into the somatosensory cortex of the brains of newborn athymic rats, with the expectation that the human cells would grow along with the rats’ cells. The somatosensory cortex is the sensory receptive part of the rats’ whiskers, which transmits signals to other brain areas to interpret signals.

Transplantation of human cortical organoids in the developing rat cortex (Source: Nature)

Human brain cells mature much slower than rat cells, and researchers had to wait at least six months for the organoids to fully integrate into rats’ brains. Based on the results of this study, the human stem cell-derived cortical organoids transplanted into the somatosensory cortex of newborn athymic rats develop mature cell types that integrate into sensory and motivation-related circuits. The team also used MRI to examine the growth of the transplanted organoid and observed cortical generation using single-nucleus profiling. When researchers stimulated the whiskers of these rats, transplanted human cells in their sensory cortices responded accordingly, indicating that these cells could effectively acquire sensory information.

In addition, to demonstrate the potential of this study for disease research, the team also grew human-brain-like organs from stem cells of three patients with Timothy Syndrome, a rare disease related to heart conditions and autism, with the expectation that they would induce symptoms similar to those of autism. Although the cells appeared no different from other brain-like organs when transplanted into the brains of rats, they did not grow as large as healthy brain-like organs, and their neurons did not undergo electrical discharge in the same way.

A Study Pushed to the Ethical Edge

However, such research is still ethically dubious to many, and it is possible that the inadvertent creation of rodent-human hybrids could harm animals. In April 2021, a panel organized by the US National Academies of Sciences, Engineering, and Medicine released a report concluding that human brain organoids are not sophisticated enough to become conscious, attain human-like intelligence or acquire other abilities that might require legal regulation. The team reported that its humanoid brain transplant did not cause seizures or memory problems in the rats and did not appear to alter the animals’ behavior significantly.

It is worth noting that the experiment of transplanting human brain-like organs into mice is by no means new. Neuroscientist Rusty Gage and his team did this pioneering work in 2018, but he transplanted the brain-like organs into adult mice rather than newborns. But because the brains of newborn mice are more adaptable to new cells than adults, they are more tolerant of transplanted human neurons. Although the transplantation procedure is still too expensive and complex to become a standard research tool in laboratories, it is an important step in exploring the complexity of the brain.

Written by Aurora Mau, translated by Richard Chau.

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