We’re getting close to growing a brain in a lab dish

A tiny version of the developing cerebral cortex—the area of ​​the brain involved in thinking, memory, and problem solving—has been grown in a lab dish with a blood vessel system that closely resembles the real thing. This cluster of cells is one of the most detailed brain organoids yet created and will advance our understanding of the brain.

Brain organoids, sometimes called “mini-brains,” are typically grown in lab dishes by bathing stem cells in a mixture of chemical stimuli that induce them to form spheres of cells. Since they were first created in 2013, these brain structures – which resemble the fetal or newborn brain – have provided fresh insights into conditions such as autism, schizophrenia and dementia.

But organoids have one major flaw: they usually start dying after a few months. This is because while a full-sized brain is equipped with a network of blood vessels to transport oxygen and nutrients, brain organoids can only absorb them from the dish in which they grow, starving the innermost cells. This limits their size and complexity, as well as how well they resemble the developing brain. “It’s a very big problem,” he says Lois Kistemaker at the University Medical Center Utrecht Brain Center in the Netherlands.

To solve this, Ethan Winkler at the University of California, San Francisco, and his colleagues grew human stem cells in lab dishes for two months to produce what they call “cortical organoids” because they mimic the developing cerebral cortex. They separately grew organoids composed of blood vessel cells and placed two of them at opposite ends of each cortical organoid. A few weeks later, the blood vessels spread evenly throughout the miniature brains.

Crucially, by imaging the organoids, the researchers revealed that the blood vessels have a hollow center, or lumen, very similar to that found in the brain. “The demonstration of vascular networks with lumens like you would find in real blood vessels is impressive,” he says Madeline Lancaster at the University of Cambridge, who was the first to develop brain organoids. “It’s a significant step.”

Previous efforts to introduce blood vessels into brain organoids failed to reproduce this important detail and typically saw the vessels spread unevenly within the organoids. What’s more, compared to previous attempts, the blood vessels in this new experiment appeared to more closely resemble the physical properties and genetic activity of those found in actual developing brains, forming an improved “blood-brain barrier”—a boundary that normally protects the brain from invading pathogens while allowing nutrients and waste products to pass through, Kistemaker says.

Together, the findings suggest that the vessels have a better chance of transporting nutrient fluid to keep the organoids alive, Lancaster says. “To make it really functional [blood vessels]they would need a way to continuously pump blood, like the heart does, and it would have to be directional, so that fresh oxygenated blood—or substitute-like blood—goes in while deoxygenated blood is taken out,” says Lancaster. “We’re a long way from that,” he says.

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