Harvard keeps lab-grown brain organoids alive for 5 years

Harvard neuroscientists have kept lab-grown human brain organoids alive for more than five years, tripling the previous record and demonstrating that these miniature models of the cerebral cortex can faithfully replicate the developmental timeline of a living human brain. The findings, published Wednesday in Nature, open new avenues for studying neurological disorders that emerge later in life and could eventually lead to therapies involving replacement of diseased brain cells.current.fas.harvard+1

A Living Clock in a Dish

The study, led by Paola Arlotta, Golub Family Professor of Stem Cell and Regenerative Biology at Harvard, examined 34 organoids — peppercorn-sized clumps each containing more than 1 million cerebral cortex cells derived from human blood samples. Combined with previous work, the team gathered data on 110 organoids and nearly 425,000 individual cells, monitoring them with single-cell RNA sequencing at eight timepoints between six months and five years.current.fas.harvard

The previous record for the oldest brain organoid, reported in 2021 by researchers at UCLA and Stanford, was 694 days — a little under two years.kuwaittimes+1

Using DNA methylation as an "age clock," the researchers found that their organoids replicated the same molecular developmental sequence documented in living human brains during gestation and the first years of life. Neurons established connections with each other and fired electrical signals that the organoids sustained for at least two years.medicalxpress

A 'Time Warp' of Development

In what Arlotta called a "crazy experiment," the team mixed cells that had been developing for a year with others only two weeks old, creating a chimeric organoid. When exposed to chemical signals, the younger cells behaved normally, producing early-stage neurons. But the older cells skipped ahead, immediately generating later-stage neurons that would normally take months to appear.kuwaittimes

"We were a little bit shocked by the results," Arlotta said. "I like to call this a 'time warp' of development — they skip ahead."current.fas.harvard

The finding indicates that organoid brain cells "recorded the passage of time and retain a memory of the developmental steps already performed," according to the Nature paper. This does not mean organoids have memories in the conventional sense, Arlotta emphasized, but rather that their developmental history is "engraved" at the cellular level.pubmed.ncbi.nlm.nih+1

Implications and Limitations

The breakthrough could help researchers study how disorders such as autism and schizophrenia emerge and progress over time, as most previous organoid studies captured only the earliest phases of brain development. Arlotta speculated that the time-warp technique could one day be used to rapidly generate specific brain cell types for therapeutic purposes.kuwaittimes+1

Scientists widely agree that organoids are not capable of consciousness or higher-order brain functions. The organoids used in this study have since been destroyed.kuwaittimes