Brain-like organelles grown in vitro from human cells with autism have shown that overactive neurons in the brain can contribute to the development of the disorder.
Organelles are artificially grown collections of cells that resemble a desired organ, and those used in the new study were designed to resemble the cerebral cortex, allowing scientists at Utah Health Sciences to study this still mysterious part of the brain.
Brain-like organelles for #autism Research Created @TheOfUHealth Scientists
The brain is the size of a seedlike organelles resemble of one wrinkle in human brain 15 to 19 weeks post-concept. To study more: https://t.co/7SLfl4xSfIrice.twitter.com/oxfxnevxky
— Inside Precision Medicine (@Inside_PM) October 6, 2022
The seed-sized “brain” was grown in the lab using stem cells from an autistic person, allowing scientists to see how neurons can differ in a person with the disorder.
The use of organelles could help researchers explore what happens in the early stages of neurological conditions, before symptoms appear, said senior researcher Yueke Wang.
To create the organelles, the team studied how the brain develops normally and induces human stem cells to follow the same path.
Stem cells started out as neuroepithelial cells, a special type of stem cell that form self-organizing structures called neural sockets in a cup.
The cells were then left to grow on their own, and over the course of several months, the structures turned into balls and increased in size and complexity at the same rate as the fetal brain had developed.
Five months later, the team found that the organelles have what looks like “the only wrinkle in the human brain as it appears in the fetus after 15-19 weeks of gestation,” according to the Utah University Health Sciences.
The structures contained a range of neurons and other cell types found in the cerebral cortex, the outermost layer of the brain involved in speech, emotion, reasoning, and other higher-level mental processes.
“We are beginning to understand how the complex neural structures in the human brain arise from simple ancestors,” Wang notes. “We can measure disease-associated phenotypes using three-dimensional organelles derived from stem cells containing genetic mutations.”
Being able to model aspects of the brain in this way gives scientists a glimpse into the inner workings of a living organ that is nearly impossible to access. Because organelles grow in labware, they can be tested experimentally in ways that living brains cannot.
The team used an innovative process to study the impact of genetic abnormalities associated with autism spectrum disorder on human brain development. They found that organelles engineered to contain lower levels of the autism-linked SHANK3 gene had distinctive features, including excessive neural activity and disruption of specific molecular pathways that cause cells to stick together.
The authors say these findings help uncover the cellular and molecular causes of symptoms associated with autism. They also show that lab-grown organelles will be useful for better understanding the brain, how it develops and what happens during illness.
However, there is controversy over human “mini brains” growing in the lab, and some scientists fear these organelles could eventually be transplanted into animals to better understand neurological disorders.
The warning comes from a Kyoto University team published in a 2021 research paper that highlights a number of ethical implications that can come from researching brain organelles.
Brain organelles, first created in 2008, are three-dimensional spheres of brain-like tissue that grow from stem cells, usually human.
Source: Daily Mail
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