Study Finds Brain Organoids Can Keep Maturing for Years in Culture

A team led by researchers at University Medical Center Utrecht has kept brain organoids growing longer than ever recorded. Over more than five years, the tissue continued to mature in ways that closely track human brain development, according to findings published in Nature. The extended lifespan gives researchers new opportunities to study neurodevelopment, model brain disorders and test potential drugs. 

The human brain keeps developing until around age 20, a process traditionally studied through donated brain tissue and animal models. Both approaches have limits: donated tissue offers only snapshots of development, while animal brains differ from human brains in cell-type composition and developmental timing. Brain organoids, grown from stem cells, offer an alternative. “These models allow us to track development over time and examine how different brain cell types emerge,” co-author Noelia Antón-Bolaños noted. Until now, most organoid studies covered only the earliest stages of development, since organoids couldn’t be kept in culture long enough to study more. 

The main obstacle was sustaining neuronal activity over years, something standard culture conditions failed to support. “By adapting the composition of the culture medium, we supported that activity, kept the neurons active, and maintained the neuronal populations for much longer,” Antón-Bolaños explained. Dedicated researchers also maintained the cultures in an isolated setting throughout the study, allowing the team to track cell types, gene expression, epigenetic changes and neuronal activity at set time points.

Multiple signs confirmed the organoids weren’t just surviving but continuing to develop: brain cell types emerged in the expected order, neurons built increasingly complex connections, and genes switched on and off on schedule. Epigenetic changes followed the same characteristic pattern seen in the developing human brain. After roughly a year, the organoids displayed features normally seen only after birth. “The cells are outside the body, yet they still follow approximately the same developmental timeline as we do—and even more closely than we had anticipated,” Antón-Bolaños added.

The team also found that older cells retained a memory of developmental time: when regrown, they produced only cell types tied to later developmental stages, though mixing them with younger cells partly restored neuron production. Because the organoids remain highly reproducible over this extended timeline, the researchers see potential for modeling conditions like autism spectrum disorder and schizophrenia, and eventually for drug testing. Next, the team plans to study how cues such as light stimulation might further improve maturation.