Romanian-born Sergiu Pasca coordinated a research team from the United States, which succeeded in implanting a type of human brain cells, called organoids, in young mice. The project aimed to study complex psychiatric disorders, such as schizophrenia, and experiment with a range of treatments.
Researchers are already practicing the technique of placing in culture, in Petri dishes, some human brain tissues obtained from stem cells. However, in the laboratory, “neurons do not reach the size they would have in a real human brain”, explained Sergiu Paşca, professor of psychiatry and behavioral sciences at Stanford University in the United States and lead author of the study published in the journal Nature.
In addition, these tissues placed in culture outside the human body do not allow studying the symptoms that a defect in their functioning generates. One solution would be to implant these human brain tissues, called organoids, into the brains of young mice. Age is important, as the brain of an adult animal stops developing, which would affect the integration of human cells.
By transplanting them into a young animal, “we found that the organoids can become quite large and vascularized” and, therefore, be fed by the blood network of the mouse, ending up occupying up to about a third of the brain hemisphere” of the animal, Sergiu Paşca further explained.
The authors of the study tested the good implantation of the organoids by blowing a current of air towards the mouse’s whiskers, which led to an electrical activity in the neurons of human origin – a sign that they played the role of receptors of an external stimulus well. Next, the researchers wanted to find out if those neurons could transmit a signal to the mouse’s body. To do this, the scientists implanted organoids that had been previously modified in the laboratory to react to blue light. Next, they trained the mice to drink water from a cannula when blue light stimulated the organoids via a cable connected to their brains. The maneuver proved effective in two weeks.
The Stanford University team finally used their new technique using organoids taken from patients diagnosed with a genetic disease, Timothy syndrome. The researchers noticed that in the brains of that mouse, the organoids grew less quickly and had less activity compared to organoids from healthy patients. In the long term, the new technique could be used to test a range of new drugs, as scientists forecast.
Professor Sergiu Paşca denied such a risk for the studied mouse, due to the rapidity with which its brain develops in relation to the human one. He qualified as a “natural barrier” the functioning of the mouse cortex, which would not have the necessary time to deeply integrate neurons of human origin.
Such a barrier could, on the other hand, no longer exist in the case of species closer to humans, says Sergiu Paşca. The Romanian-American researcher opposes the use of this method on primates. He emphasizes the “moral imperative” that people should be able to better study and possibly treat psychiatric disorders, while taking into account the proximity to humans of the animal model used. “Human psychiatric disorders are very specific to humans. That’s why we have to carefully reflect (…) to what point we want to work on some of these models”, warned Sergiu Paşca.
Who is Sergiu Pasca?
Sergiu Paşca, born in Cluj-Napoca on January 30, 1982, is a Romanian-American doctor and scientist, who currently works as a professor of psychiatry and behavioral sciences at Stanford University in the United States.
Sergiu Paşca spent his childhood in Aiud during the last years of communism in Romania. He showed a special interest in chemistry from an early age and set up his first scientific laboratory at the age of 11 in the basement of his parents’ house.
In the last year of high school, he won a prize at the national chemistry Olympiad, thus obtaining a scholarship and the right to enroll in any college he wanted in our country. In 2001, he enrolled at the “Iuliu Haţieganu” University of Medicine and Pharmacy in Cluj-Napoca. At the same time, he studied electrophysiology at the Max Plack Institute for Brain Research in Frankfurt.
After obtaining his medical degree in 2007, Sergiu Paşca enrolled in post-doctoral studies at Stanford University in 2009. At this American university, he developed methods to obtain neurons from induced pluripotent stem cells (iPSCs) and to use those neuron cultures with the aim of identifying cell phenotypes associated with brain diseases, such as Timothy Syndrome and Dravet Syndrome.