Science Writing (EFE).- Organoids are tiny 3D structures derived from stem cells that mimic organ function and could hold the key to studying disease. Today, scientists have succeeded in implanting this human brain tissue into the brains of rats, overcoming significant previous limitations.
The description of the new method is published in the journal Nature, in an article in which the authors describe that brain tissue derived from human stem cells was able to integrate into the brains of newborn rats, influencing their behavior.
The results could improve the ability to produce realistic models of human neuropsychiatric diseases.
Brain organoids represent a promising platform for modeling human development and disease; however, organoids grown outside the body lack the connectivity that exists in real organisms.
This limits their maturation and prevents them from integrating with other neural circuits that control behavior. It therefore limits the ability of organoids to model genetically complex and behaviorally defined neuropsychiatric diseases.
Previous research attempted to implant human brain organoids into the brains of adult rats, but these cells failed to mature.
Now, Sergiu Pașca of Stanford University in California and his team have transplanted human brain organoids into the somatosensory cortex of newborn rat brains, the area responsible for receiving and processing sensory information, such as the touch, whole body. .
Links between human cells and animal behavior
They found that the organoids matured, partially integrated into neural circuits, and demonstrated their functionality in rodent brains, the journal summarizes.
This integration made it possible to establish links between human cellular activity and learned animal behavior, showing that the transplanted neurons could modulate rat neuronal activity and lead to reward-seeking behavior.
Additionally, a group of organoid neurons showed activity when the researchers flicked the rats’ whiskers, indicating that the transplanted neurons can respond to sensory stimulation.
The team, which also included scientists from the Swiss Federal Institute of Technology (ETH) Zurich, also found that transplanting cells from three patients with Timothy syndrome – a serious genetic condition associated with heart problems – revealed specific neuronal abnormalities.
Human brain development and disease
This demonstrates the ability of this transplant technique to reveal previously unknown features of the disease, say the authors.
“This technique could represent a powerful resource to complement laboratory studies of human brain development and disease,” the scientists suggest, noting that future research may uncover features of disease in cells derived from patients who would otherwise , would be elusive.
Núria Montserrat, ICREA research professor at the Institute of Bioengineering of Catalonia, believes that the study represents “a very important advance” in the field of brain organoids.
To date, brain organoids have provided fundamental knowledge for understanding the embryonic development of this organ, as well as understanding the aspects related to the appearance of certain pathologies.
All these advances were limited by important aspects, such as the lack of connectivity of neural circuits in a way similar to what happens in the native organ, recalls this scientist, who was not involved in the study.
“In order to overcome these limitations, researcher Pașca’s group has developed a methodology that allows the transplantation of mini-brains derived from healthy human cells and cells that capture the genetic basis of a rare congenital disease (Timothy syndrome)” says he at the Science Media Center Spain.
“Although the study has important implications (…), it also shows that the methodological approach carried out has important limitations, given that the differences between the nervous systems of humans and rats can give rise to misinterpretations (as pointed out by researchers in the conclusions of their study).
Web edition: Marina González