Stem Cell Derived Mini Brain that Engenders Blood Vessels
The human cerebral cortex defines us as who we are. Its development and function underlie complex human cognitive behavior, while its malfunction or degeneration causes countless neurological and psychiatric diseases. Additionally, shielded by by our thick skulls and swaddled in layers of protective tissue, the human brain is extremely difficult to observe in action.
And in both these cases- emerges a saviour- the mini brain. Lab-grown miniature brains are poised to shake up drug testing for everything from Alzheimer’s disease to Zika. Reported early last year, each bundle of human brain cells is so tiny that it could fit on the head of a pin.
With induced pluripotent stem cells (iPSCs) derived from a readily-accessible skin sample from patients, it’s possible to generate three-dimensional balls of cells that mimic particular parts of the brain’s anatomy. But then, as with any new tech, there is always room for improvement. One thing that most mini-brains lack is their own system of blood vessels, or vasculature.
Enter miniature lab-grown brain cells capable of sprouting their own blood vessels.
“The whole idea with these organoids is to one day be able to develop a brain structure the patient has lost made with the patient’s own cells,” UC Davis vascular neurosurgeon Ben Waldau says.
The breakthrough could allow the brains to survive for longer, thanks to the vital oxygen and nutrients supplied by the vessels, and could encourage them to keep growing.
Using brain membrane cells taken from one of his patients during a routine surgery, the team coaxed them first into stem cells, then some of them into the endothelial cells that line blood vessels’ insides. The stem cells they grew into brain balls, which they incubated in a gel matrix coated with those endothelial cells.
After incubating for three weeks, they took a single organoid and transplanted it into a tiny cavity carefully carved into a mouse’s brain. Two weeks later the organoid was alive, well—and, critically, had grown capillaries that penetrated all the way to its inner layers.
These so-called brain balls are the first to become vascularised (meaning they’re the first to sprout vessels), with previous experiments resulting in mouse blood cells infiltrating the small cerebrums.
However, scientists still aren’t certain if the blood this network of vessels carries is human or rodent.