Human “mini-brains” that contain 80 per cent of the cell types in a 40-day-old fetal brain have been created by fusing different organoids together.
“We’re getting to the point that we are getting closer to the fetal brain,” says at Johns Hopkins University in Maryland. The reason for doing this is to create organoids that are better suited for studying conditions such as autism and schizophrenia, which is hard to do in animals, she says.
“If we want to do disease, toxicology or environmental studies on a brain in a dish, we should get it as close as possible to the [human] brain,” says Kathuria. “I would say it’s a little better than a mouse, a little less than a human. It’s somewhere in between.”
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These structures, which the team call multi-region brain organoids, are still nowhere near a real human brain, says Kathuria. “We’re very far away from getting to the point where we have to worry that this is developing consciousness or pain or intelligence.”
In the past two decades, it has become possible to grow miniature versions of many human organs by putting stem cells in the right chemical and physical conditions. In 2013, a team that included at the MRC Laboratory of Molecular Biology in Cambridge, UK, grew human brain organoids for the first time.
Both animal and human brain organoids are now widely used for research. A few groups are even trying to turn them into living artificial intelligence processors for carrying out various tasks.
However, in addition to containing far fewer neurons overall, brain organoids are also made up of only a small fraction of the cell types found in a normal brain, making them more like miniature versions of specific brain regions than the entire organ.
They also never grow more than a few millimetres wide because, with no blood vessels to supply oxygen, the cells in the middle start dying once they grow larger.
Kathuria’s team is one of several that is trying to solve these issues by fusing different organoids together. The researchers generated two kinds of brain organoids from cerebral and hindbrain cells, plus an epithelial organoid, as these cells form blood vessels, among other things.
After 20 days, the three organoids – each less than a millimetre across – were brought into contact, resulting in fusion. Some cells moved from one organoid into another, so they intermingled to some extent.
The team repeated the experiments with stem cells from three individuals, but each fused organoid was derived from a single person’s cells.
Fusing organoid types in this way is certainly an exciting approach, says Lancaster, who wasn’t involved with the study. But other teams have created fused organoids – sometimes called assembloids – with a similar level of sophistication, says Lancaster.
In addition to creating most of the cell types seen in early fetal brains, the team also saw the early stages of epithelial cells sprouting into blood vessels, says Kathuria. The team is now working on providing some form of fluid movement to encourage their development. “We’re collaborating with engineers to start generating the flow in the system,” she says.
So far, no team has managed to create brain organoids with working blood vessels, says Lancaster.
At some point, the scientific community will have to decide on a cut-off point beyond which further development of brain organoids is unethical, says Kathuria. But it might be 10 years before the technology gets to that stage, she says.
bioRxiv
