AILSA CHANG, HOST:
They are known as mini-brains or brain organoids, and they're changing the way scientists study brain development and disorders like autism. But new research finds that these tiny clusters of cells, which are grown in the lab, differ from actual brain tissue in some important ways. NPR's Jon Hamilton reports.
JON HAMILTON, BYLINE: Dr. Arnold Kriegstein uses brain organoids in his lab at the University of California, San Francisco. And he knows that under the right conditions, immature brain cells in a dish will assemble themselves into a three-dimensional structure that looks a lot like human brain tissue. But he and his lab wondered whether the cells in an organoid were really just like the ones in a developing brain.
ARNOLD KRIEGSTEIN: We wanted to see whether the organoids that we and others have been using to model normal brain development as well as disease actually represented the cell types faithfully.
HAMILTON: So Kriegstein's team took a close look at the cells in organoids that mimic the brain's outer layer or cortex.
KRIEGSTEIN: We compared them to our database and were surprised to see that there were some dramatic differences that hadn't been reported before.
HAMILTON: The organoids did have the major cell types found in cortex, but Aparna Bhaduri, a postdoc in Kriegstein's lab, says they were a little off.
APARNA BHADURI: In the normal brain, you have very clear and precise different types of cells. And what we're seeing in the organoid is more of a confused identity.
HAMILTON: The cells looked immature, like they hadn't decided what kind of cells to become. They also showed signs of metabolic stress, as if they'd been undernourished. And Madeline Andrews, another postdoc in Kriegstein's lab, says the team found a reason.
MADELINE ANDREWS: Something about the artificial nature of, you know, the media or the conditions that they're being grown in is actually resulting in this stress.
HAMILTON: When the team took cells from an organoid and transplanted them into a mouse brain, the stress and identity problems went away. Kriegstein says the new study does not question the value of organoid research, but he says scientists should proceed with caution.
KRIEGSTEIN: It's far too early to start using organoids as examples of normal brain development because we just don't know how well they really represent what's going on in utero.
HAMILTON: Dr. Guo-Li Ming, a brain scientist at the University of Pennsylvania, agrees that organizations have limitations.
GUO-LI MING: There is a concern, but I'm not concerned too much about it.
HAMILTON: Ming says her lab has also detected stress in organoid cells, but she's not sure this explains the cells' identity problems.
MING: One of the things that hasn't been established, I think, is whether this stress is indeed causing limited maturation in the organoids.
HAMILTON: Scientists are already working on ways to reduce stress in brain organoids and make them more like actual brain tissue. And Ming says they're still the only good option for learning how a human brain develops before birth.
MING: Brain organoids is the best approach for allowing us at least to understand what's happening.
HAMILTON: The new research appears in the journal Nature.
Jon Hamilton, NPR News.
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