More realistic brain organoids
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More realistic brain organoids

Using cells taken from the blood and reprogrammed into stem cells. [1]Researchers at the University of Saskatchewan were able to produce brain organoids with a diameter of approximately three millimeters. These ” mini brains » differ in that they are made up of four different types of brain cells [2], whereas most cerebral organoids are composed of neurons only (see Brain Organoids for the study of neurodevelopmental disorders). They published their work in a magazine Frontiers of Cellular Neuroscience [3].

A more accurate “model” to aid in diagnosis

These organelles reflect ” more devoted “The adult brain,” says Tyler Wenzel, the first author of the study. Thus, they could be used to diagnose pathologies such as Alzheimer’s disease from patient blood samples. They can also be used to test the effectiveness of drugs in patients, thereby reducing the time needed to access tailored treatment, for example in the case of depression. Now the scientist plans to expand the trials to more patients.

Team from Cincinnati Children’s Hospital Medical Center for his part developed the first ” mini brain “a person with a blood-brain barrier (BBB)” fully operational »[4]called ” BBB [5] assembly “. These organelles mimic the development of the human neurovascular system, providing an accurate representation of the barrier in growing and functioning brain tissue. “(cf. Researchers are studying the vascularization of brain organoids). These results were published in the journal Cell Stem cell [6].

The lack of an authentic human BBB model has become a serious obstacle to the study of neurological diseases. “explains lead author of the study Ziyuan Guo. Indeed, “The animal models we currently use in research do not accurately reflect human brain development and BBB functionality. “.

Organelle Assembly

BBB assembloids ” combines two different types of organoids: brain organoids, which mimic human brain tissue, and blood vessel organoids, which mimic vascular structures.

Over the course of about a month, these separate structures [7] merged into a single sphere with a diameter of just over 4 millimeters.

Although they” recreate many of the complex neurovascular interactions observed in the human brain “, these ” assembleloids “are not complete models of the brain. For example, they lack immune cells and have no connections with the rest of the nervous system.

To demonstrate the potential usefulness of ” new builds “, the researchers used a stem cell line obtained from patients with a rare brain disease called cerebral cavernoma. [8]. But scientists are considering numerous applications, from finding new treatments to developing biomaterials, including assessing the toxicity of chemical components (see “Brain Organoid Research: A Question of Conscience”).

[1] iPS cell method

[2] Neurons, microglial cells, astrocytes and oligodendrocytes.

[3] Tyler J. Wenzel et al., Brain organoids engineered to generate glia and neural networks display human-specific proteoforms after 90 days of culture, Frontiers of Cellular Neuroscience (2024). DOI: 10.3389/fncel.2024.1383688

[4] ” Unlike the rest of our body, the brain’s blood vessels have an extra layer of tightly packed cells that severely limits the size of molecules that can pass from the bloodstream into the central nervous system.. » « A properly functioning barrier maintains brain health by preventing harmful substances from entering and allowing essential nutrients to reach the brain. However, this same barrier prevents many potentially beneficial drugs from reaching the brain. In addition, some neurological disorders occur or worsen when the blood-brain barrier does not form properly or begins to break down. »

[5] For Blood-brain barrier

[6] Lan Dao et al., Modeling the formation of the blood-brain barrier and cerebral cavernous malformations in human PSC-derived organoids, Cell Stem cell (2024). DOI: 10.1016/j.stem.2024.04.019

[7] brain organoids with a diameter of 3 to 4 millimeters and blood vessel organoids with a diameter of approximately 1 millimeter.

[8] ” This genetic disorder, characterized by a breakdown in the integrity of the blood-brain barrier, results in the formation of clumps of abnormal blood vessels in the brain, often resembling raspberries. This disease significantly increases the risk of stroke. »

Sources: Medical Xpress, University of Saskatchewan (May 14, 2024); Medical Xpress, Cincinnati Children’s Hospital Medical Center (May 20, 2024)

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