Developing Miniature Brain Organoids with Blood Vessels
Most brain organoids lack blood cells, limiting their use
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A breakthrough in the field of neuroscience has led to the successful growth of a tiny version of the developing cerebral cortex in a lab dish, complete with a system of blood vessels that closely resembles the structure in a real brain. This intricate clump of cells marks a significant advancement in the creation of brain organoids and is poised to enhance our understanding of the complexities of the brain.
Brain organoids, often referred to as “mini-brains”, are typically cultivated in laboratory settings by exposing stem cells to specific chemical signals, prompting them to form cell clusters resembling various brain regions. Since their inception in 2013, these miniature brain structures, resembling fetal or newborn brains, have provided valuable insights into neurodevelopmental disorders such as autism, schizophrenia, and dementia.
However, a major limitation of organoids is their short lifespan, usually lasting only a few months. Unlike fully developed brains that have a network of blood vessels for oxygen and nutrient transport, organoids rely on external nutrient sources, leading to the eventual death of inner cells due to starvation. This constraint hampers the size, complexity, and accuracy of organoids in mimicking the developing brain, posing a significant challenge for researchers.
To address this critical issue, Ethan Winkler and his team at the University of California, San Francisco, embarked on a groundbreaking experiment. They cultured human stem cells for two months to create “cortical organoids”, resembling the developing cerebral cortex, and separately grew blood vessel organoids. By strategically placing these blood vessel structures at opposite ends of the cortical organoids, the researchers observed the gradual formation of a network of blood vessels throughout the miniature brains over the following weeks.
Importantly, imaging studies revealed that these engineered blood vessels featured a hollow center, or lumen, closely resembling the natural blood vessels in the brain. This unique characteristic sets this study apart from previous attempts to integrate blood vessels into organoids, which often lacked this crucial detail. Additionally, the vessels in this experiment exhibited physical properties and genetic activities more akin to those found in real developing brains, contributing to the formation of an enhanced “blood-brain barrier” that safeguards the brain from pathogens while facilitating nutrient exchange.
While these findings represent a significant advancement in the field of brain organoid research, Madeline Lancaster of the University of Cambridge emphasizes that there is still a long way to go before achieving fully functional blood vessels within organoids. The ability to continuously pump blood through these vessels in a directional manner remains a key challenge that researchers must address in future studies.
Overall, the successful integration of blood vessels into brain organoids opens up new possibilities for studying brain development and disease mechanisms in a more accurate and detailed manner. This innovative approach paves the way for future advancements in neuroscience and holds promise for unraveling the complexities of the human brain.
