In a world first, scientists were able to grow cerebral organoids, which are lab-grown and three-dimensional mini brains, from fetal brain tissue of humans.
Cerebral Organoid Minibrains Grown From Fetal Brain Tissues
The novel organoids grew to become grain-sized. It also holds various cell types that self-organize themselves into intricate 3D structures.
On top of this, the researchers also triggered brain tumor growth in the minibrains and examined the response of the tumors to current cancer drugs.
These cerebral organoid minibrains mirror the crucial aspects of function and development of human brains that are full-sized. Previously, minibrains have been grown from the stem cells of humans. However, they were never directly derived from brain tissue that was already formed. Hence, the novel organoids lead to great possibilities.
The novel developments were published in the "Human fetal brain self-organizes into long-term expanding organoids" study.
For the creation of the novel minibrains, the researchers took brain tissue samples from deceased fetuses that were around 12 to 15 weeks old. These were offered by anonymous donors.
The researchers separately grew tiny samples of each tissue on small plates. They made use of certain nutrients and growth factors. Each of the samples was shaken continuously as it grew in order to make sure that all the cells in them were chemically exposed. They were also not granted any physical scaffolding to help them with their growth.
After roughly four to eight days, the researchers observed that several organized 3D structures were formed. Later on, these matured into organoids that had the appearance of tissue.
The minibrain outputs had various cell types, including outer radial glia. The tissues also made their own extracellular matrix proteins. These served as scaffolding and helped 3D organizations. This could allow scientists to look deeper into how cell environments could affect how they develop.
For this initial experiment, the cerebral organoid minibrains were grown for six months. Interestingly, the scientists were able to grow several minibrains from just one tissue sample.
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Derived From Tissues, Not Stem Cells
Dr. Hans Clevers, a co-senior author of the study and a professor of medicine from Utrecht University, explains that, until now, they were only to have organoids derived from the majority of the human organs but not the brain. Dr. Clevers expresses excitement regarding how they were able to bypass such hurdles.
According to the researchers, these minibrains could complement some organoids that were derived from stem cells and facilitate novel and distinct ways for studying brain disease and health.
As stem cells need to be coaxed in order for them to resemble various brain parts, tissue that is plucked from the brain is able to capture its tissues at certain stages of development. Moreover, while stem cells need to be granted scaffolding for them to grow on, brain tissues are capable of making their own.
Delilah Hendriks, the first author of the study and an affiliated group leader of the Princess Máxima Center for Pediatric Oncology, explains that these novel fetal-tissue-derived cerebral organoids can grant new insight regarding what affects the various brain regions and what leads to cellular diversity.
In the past, minibrains have been engineered by scientists using pluripotent stem cells. These are primitive cells that exhibit the potential to turn into any kind of cell if they are offered specific chemical cocktails. Such minibrains have been seen to be useful when it comes to studying related disorders as well as development.
However, brain-tissue-derived minibrains could offer novel insights regarding cell behavior and characteristics that are unique to the brain, as noted by the researchers.
Moving forward, the researchers hope to make more complex minibrain versions and potentially develop them from tissues of fetuses at various developmental stages. They also want to do so from diseases tissues that may capture the defects of the brain linked to mortality of infants.
Similar to other human brain models, specialized ethical frameworks and active talks with donors and the scientific circle are necessary before further experiments are made with the organoids.
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