What are brain organoids?
Often called “mini brain models”, brain organoids are 3D models of the brain that are grown in the laboratory to study mechanisms of disease. They are described as “mini” because they are grown in a Petri dish and mainly observed under the microscope. Unlike our actual brains, they cannot think or feel, but they are a powerful tool to understand what happens in the brain at a molecular and cellular level.
How are brain organoids made and grown?
To grow brain organoids, it all starts with a small skin biopsy sample from a patient or a healthy individual. This sample contains skin cells, which can be reprogrammed back into stem cells, known as induced pluripotent stem cells (iPSCs). This process works by providing the cells with the right nutrients and signals at the right time. This breakthrough was made by Japanese researcher Shinya Yamanaka, who was even awarded the Nobel Prize for this discovery! Once iPSCs are created, they can self-organise into groups of cells which resemble the developing brain in a dish, forming what we call a brain organoid.
What does “feeding” organoids mean? Just like the cells of our bodies, the cells that make up organoids need nutrients and developmental signals to survive and flourish. This is why researchers prepare liquid “media” containing everything the cells need and regularly replace it, from every day to every few days. Organoids also need a carefully controlled environment and are usually kept in an incubator at 37 °C, the same temperature as the human body.
Sophie “feeding” her brain organoids in the lab.
How does this help us understand dementia and FTD?
Frontotemporal dementia (FTD) is a neurological condition with a biological basis in the brain. Much of what we know about the mechanisms of FTD comes from years of research, not only involving patients but also animal models and laboratory-based cell models such as brain organoids. Models of FTD such as brain organoids allow us to study brain-like cells without needing to access a person’s brain itself, which is incredibly valuable! These organoids contain not only neurons but also important support cells, such as astrocytes. Many different processes can be studied, including genetics and build-up of specific proteins, which is a key feature of many neurodegenerative diseases, including FTD. Ultimately, the goal of using brain organoids is to identify new treatment targets and test potential therapies, helping us understand how they might work in people with FTD.
Sophie’s work on GRN organoids
Sophie is a second-year PhD student who uses brain organoids to study a genetic form of FTD, caused by mutations in the gene GRN. She works with cells from patients affected by this form of FTD (GRN-FTD), as well as from healthy individuals, to grow brain organoids that she can compare to identify disease-specific changes. These organoids resemble the forebrain, a part of the developing brain which later gives rise to many regions including the cerebral cortex, which is central to FTD. Mutations in GRN have been shown to lead to reduced levels of a protein called progranulin. This reduction is linked to the build-up of another protein, TDP-43, which is thought to be toxic to brain cells and ultimately leads to FTD. These decreases and increases in protein levels can be studied in brain organoids using a variety of laboratory techniques. Sophie’s brain organoids therefore provide an exciting window into the biological processes that may be happening in the brains of individuals living with FTD.
Sophie also has a science account where you can learn more about what it is like to work with brain organoids in the lab. You can find it here!
An incredible image of a brain organoid, taken by Sophie on the microscope!
Luna Nordenström, on behalf of the FTD talk team.
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