Revitalizing Brain Organoids: A Breakthrough in Vascular Integration Imago/Alamy
A pioneering advancement has been made in growing a miniaturized version of the developing cerebral cortex, crucial for cognitive functions like thinking, memory, and problem-solving, complete with a realistic vascular system. This advancement in brain organoids offers unprecedented insights into brain biology and pathology.
Brain organoids, often referred to as “mini-brains,” are produced by exposing stem cells to specific biochemical signals in a laboratory setting, encouraging them to form self-organizing cellular spheres. Since their inception in 2013, these organoids have significantly contributed to research on conditions such as autism, schizophrenia, and dementia.
However, these organoids have a significant limitation: they typically start to deteriorate after only a few months. This degradation occurs because a full-sized brain has an intricate network of blood vessels that supply essential oxygen and nutrients, while organoids can only absorb these elements from their growth medium, leading to nutrient deprivation for the innermost cells. “This is a critical issue,” remarks Lois Kistemaker from Utrecht University Medical Center in the Netherlands.
To mitigate this issue, Ethan Winkler and researchers at the University of California, San Francisco, devised a method to cultivate human stem cells for two months, resulting in “cortical organoids” that closely resemble the developing cerebral cortex. They then introduced organoids composed of vascular cells, strategically placing them at either end of each cortical organoid, facilitating the formation of a vascular network throughout the mini-brain.
Crucially, imaging studies revealed that the blood vessels in these mini-brains possess hollow centers, or lumens, akin to those found in natural blood vessels. “The establishment of a vascular network featuring lumens similar to authentic blood vessels is impressive,” states Madeline Lancaster, a pioneer in organoid research at the University of Cambridge. “This represents a significant progression.”
Past attempts to incorporate blood vessels within brain organoids have failed to achieve this crucial detail; previous studies typically resulted in unevenly distributed vessels throughout the organoids. In contrast, the blood vessels formed in this new experiment exhibit properties and genetic activities more closely aligned with those in actual developing brains, thereby establishing a more effective “blood-brain barrier.” This barrier protects the brain from harmful pathogens while permitting the passage of nutrients and waste, according to Kistemaker.
The implications of these findings indicate that blood vessels are crucial for delivering nutrient-rich fluids necessary for sustaining organoids. Professor Lancaster emphasizes, “To function properly, blood vessels, similar to the heart, require a mechanism for continuous blood flow, ensuring that deoxygenated blood is replaced with fresh, oxygen-rich blood or a suitable substitute.”
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Source: www.newscientist.com

