Brain organoids, kept alive more than five years, matured like human brains

Amazing stuff! This could be a breakthrough!

"... scientists feared ruining their oldest brain organoids. Instead, the tiny models kept developing, revealing remarkable internal clock"

"... ‘Mini Brains’ Offer Major Breakthrough in Neural Research

In a new research milestone, scientists have kept human brain organoids—tiny, lab-grown neural tissue clusters—alive and developing for up to five years, a dramatic time extension that unlocks new opportunities to investigate neural development, disease, and potential treatments ..."

From the abstract:

"The human brain develops and matures over an exceptionally prolonged period of time that spans nearly two decades of life. Processes that govern species-specific aspects of human postnatal brain development are difficult to study in animal models.

While human brain organoids offer a promising in vitro model, they have thus far been shown to largely mimic early stages of brain development.

Here we develop human brain organoids for 5 years in culture, optimizing growth conditions to extend excitatory neuron viability beyond previous limits. Using maturation-associated modules derived from endogenous human brain, we show that brain organoids transcriptionally age with cell type specificity over years in culture.

Whole-genome methylation profiling reveals that the predicted epigenomic age of organoids correlates precisely with time spent in vitro, and parallels epigenomic ageing in vivo.

Notably, we show that in chimeric organoids generated by mixing neural progenitors of different ages, old progenitors rapidly produce late neuronal fates, skipping the production of earlier neuronal progeny, therefore showing that progenitors that age in organoids retain a memory of the time spent in vitro.

The data indicate that human brain organoids can continue to mature and record the passage of time over many years in culture."

Stat Daily Recap

Johns Hopkins Bloomberg School of Public Health: Global Health NOW

‘Mini brains’ kept alive for years appear to age like real brains "Miniature models of the human brain can be kept alive for years, allowing scientists to study neural development and brain diseases"

Lab-grown brain ‘organoids’ set longevity record (original news release) "Researchers show that brain cells cultured in a dish can mimic normal cerebral development and even retain “memory” of their own histories"

Scientists kept brain organoids alive for years. Then they looked inside | STAT "Eraser-sized balls of tissue could aid research on early stages of neurological diseases"

Human brain organoids record the passage of time over multiple years (open access)

Fig. 1: Cortical organoids undergo progressive maturation during long-term culture.

Fig. 3: Activity-permissive medium enhances the maturation of cortical organoids.