Researchers have grown brain organoids that include ” a wide variety of cell types from multiple people “The aim is to help understand why the brain’s response to drugs differs from one person to another. This work was published in the journal Nature [1].
Previously other teams had made 2D sheets of brain cells from multiple human donors, but this is the first work to report 3D systems. robust enough for research ». And ” a true technical tour de force », Estimates Tomasz Nowakowski, a biologist at the University of California in San Francisco, who was not involved in the study.
Ces « chimerical cultures “, which the authors have named ” chimeroids », combine cells from five donors. In the future, they could accommodate cells from hundreds of people.
A technical challenge
Cerebral organoids are “ particularly slow to grow and difficult to use “, and researchers are looking for better ways to make them. One approach is to combine cells from multiple donors into a single organoid. However, because the starting stem cells grow at different rates, the fast-growing lines inevitably take over.
The trick, according to Harvard biologist Paola Arlotta and her colleagues, is to first make a set of organoids from a single donor. As they mature, the cells in all the organoids adopt similar growth rates. In ” homogenizing » then these structures and by grouping the cells, it is possible to cultivate a “ organoïde composite “. THE ” chimeroids ” developed in this study reached a size of about 3 to 5 millimeters after three months and contained the same types of cells found in fetal cortical tissue.
A first search
As part of this research, the team treated the “ multi-donor organoids » with neurotoxic drugs.
Ethanol, which causes fetal alcohol syndrome, reduced the number of cells from one donor’s cell line. This donor’s cells grew faster when they were combined with valproic acid, an anti-epileptic drug associated with an increased risk of autism spectrum disorders in children who were exposed to it in utero.
However, further work is needed to ensure that the effects observed in chimeric models come from the genetics of a given cell line, rather than an interaction between cells very close to each other, warns Robert Vries , CEO of the Organoid Research Society HUB Organoids in Utrecht.
Editor’s note: : To carry out this research, the scientists used induced pluripotent stem (iPS) cells, which do not pose the ethical problems of human embryonic stem cells. However, the production of human brain organoids raises ethical questions in itself (see Lab-grown mini-brains: a problem of conscience?).
[1] Antón-Bolaños, N., Faravelli, I., Faits, T. et al. Brain Chimeroids reveal individual susceptibility to neurotoxic triggers. Nature (2024). https://doi.org/10.1038/s41586-024-07578-8
Source : Nature, Asher Mullard (26/06/2024) – Photo : iStock
