Tiny versions of the cerebral cortex, a brain region involved in thinking and memory, have been grown for five years, making them the longest-lived brain organoids that have been studied in detail. Their genetic activity also mimicked that typically seen in the brain of a 4-year-old child, suggesting that the organoids could sense time passing.
鈥淭his demonstrates for the first time that not only can human brain organoids be grown for about five years, but they also show an ageing profile that corresponds with that of the developing brain of a similar age,鈥� says at the University of Cambridge, who wasn鈥檛 involved in the study.
Brain organoids are clumps of brain cells grown in a lab dish. They are created by bathing stem cells in chemicals that coax them to form clumps resembling fetal brains. Studying them has already provided insights on autism and conditions like dementia. But the expense and manual labour involved means they are usually only grown for a few months, says Lakatos.
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In 2021, researchers reported growing , with these structures mimicking the cerebral cortex from its development during pregnancy to nearly one year after birth.
Now, at Harvard University and her colleagues have analysed the genetic activity of five-year-old cortical organoids grown from human stem cells. The team has grown the same kind of organoids for seven years, but there are too few of these older organoids to reliably analyse them, she says.
The researchers analysed the genetic activity and epigenetic marks 鈥� chemical tags added to DNA that regulate gene activity and shift with age 鈥� in cells within the five-year-old organoids. When comparing these measurements against those recorded from the brains of fetuses in previous research, they found that, at three to six months, the organoids resembled the fetal brain at around three to six months post-conception.
With time, the organoids resembled the later stages of brain development, with the activity of five-year-old organoids mimicking that seen in the cerebral cortex of a typical 4-year-old child. 鈥淭hey were recording the passage of time in their epigenetic signatures [and gene activity],鈥� says Arlotta.
Such long-lived organoids could offer a way to study how autism and conditions such as epilepsy emerge during the later stages of brain development, says Lakatos. Arlotta says she and her colleagues are using their organoids for this purpose, as well as to screen for drugs that may be able to alter the progression of conditions like epilepsy.
Other groups of researchers won鈥檛 be readily able to do this, due to the challenges of growing organoids, says Lakatos. Finding ways to speed up organoid ageing will be important for research, he says.
Nature
