A team from Stanford University, led by Romanian researcher Sergiu Pașca, has successfully transplanted human brain cells into the brains of mice. The experiment aims to understand and develop new treatments for diseases such as schizophrenia, epilepsy, cerebral palsy, intellectual disability, and rare forms of dementia.
The controversial study is coordinated by the Romanian professor of psychiatry and behavioral sciences at Stanford University Sergiu Pașca, as reported by The Guardian.
Scientists transplanted human brain cells grown in the laboratory into genetically modified animals born without a cortex or hippocampus. They created space for human tissue to develop inside the rodents' skulls.
The procedure now allows researchers to extract cells from patients with brain conditions, transform them into brain tissue in the laboratory, and cultivate this tissue in living animals. The animals can then be studied to observe how the condition establishes itself in human brain tissue and how medications could treat these diseases.
"We have made intense efforts to find therapeutic solutions for these conditions, but the reality is that, in psychiatry and neurology, we have lagged behind any other branch of medicine and have fewer therapeutic options than any other branch of medicine," said Professor of Psychiatry Sergiu Pașca.
"This may be due to the complexity of the human brain, but also to the fact that it is inaccessible. To a large extent, our goal has been to make certain aspects of human brain development and function accessible for research," he added.
This study represents the latest achievement in the field of neuronal organoids, where human brain cells, grown in the laboratory, organize into tiny but complex structures that mimic some of the characteristics of real brains, according to the British newspaper.
Although they have revolutionary potential for neurological medicine, organoids have raised ethical concerns - especially regarding the possibility that these tissue clusters may become conscious or feel pain, as well as the condition of the animals in which such structures have been implanted.
Pașca stated that the project has been subject to rigorous ethical monitoring from the outset.
How Mice with Modified Brains Behave
In a previous study, the Stanford team transplanted human neurons into the brains of rats. The tissue integrated and connected to the animals' brain circuits, but insufficient space significantly limited the development of human tissue.
To address this issue, researchers genetically modified mice to inhibit the development of key brain regions: the cerebral cortex and the hippocampus. Surprisingly, the mice survived, as the remaining parts of the brain took on new functions. Although they appear normal, these mice exhibit cautious movements and weaker memory.
Pașca described in an article published in the journal Nature how human brain organoids were injected into the mice, created by reprogramming donated skin cells:
- Newborn mice received multiple injections - each containing approximately 100,000 human brain cells - into the space where their own brain tissue was missing.
- In total, the rodents lacked about 14 million of their own brain cells, ending up with approximately 4 million human cells - representing half the brain volume.
- Three months after the surgery, the human tissue had connected to the mouse's circulatory system and almost completely filled the cavity, occupying approximately half of the rodent's brain size.
- Some of the human neurons established connections with the mouse's brain cells and spinal cord.
- The human neurons were not structured or connected in the same way as in humans, and the brain tissue was immature, corresponding to the mid-stage of human pregnancy.
- Tests on these mice with human brain tissue ("xenocortical") showed that the animals did not acquire enhanced abilities following the transplants, but their unsteady gait and cognitive issues slightly improved.
To demonstrate how these mice could provide valuable information about human brain conditions, researchers exposed some of the animals to an atmosphere with low oxygen levels for five hours. The experiment highlighted the vulnerability of human nerve cells to oxygen deprivation - a condition that can cause cerebral palsy during pregnancy and birth.
Scientists found that the human brain tissue in the mice contained rare cells, known as von Economo neurons, which had previously only been observed in post-mortem examinations. These cells are among the first to disappear in cases of frontotemporal dementia - a rare form of the disease that Pașca now hopes to study using mice with transplanted human cortical tissue.
A Sensitive Subject
Prof. Madeline Lancaster, head of a research group at the MRC Laboratory of Molecular Biology in Cambridge, stated that this method is most suitable for addressing questions related to conditions and treatments that require the use of a complete animal organism. "It is not very clear to me to what extent this approach will improve our understanding of human brain development, as the process is quite artificial and completely different from the natural way the brain develops," she noted.
Many researchers working with brain organoids cultivate them in vitro, meaning in laboratory dishes. There is hope that they will help reduce the number of animals used in research. "It is clearly a sensitive subject from an ethical point of view; there must be a very valid reason to resort to such experiments on animals, a necessity that does not arise in most scientific research directions," Lancaster added.
T.D.