Cell-culture brain models called organoids can be used to study far more advanced stages of neurodevelopment than researchers once imagined, according to new research.
A team funded by the National Institutes of Health (NIH) reports that organoids were sustained for almost six years—far longer than previous efforts. The findings, detailed in a recent paper published in Nature, showed that a developmental clock similar to the one governing real brains also appears to govern organoid maturation.
The work could significantly expand researchers’ ability to study later stages of human brain development and neurological conditions that emerge over longer periods.
Organoids Explained
Organoids have been a major and growing tool in neurological research. They consist of small cell cultures arranged into 3D models of human brain tissue. Typically, these have been limited to only basic reconstructions, yet the new work significantly advances their modeling capabilities by expressing much later-stage brain development attributes.
Significantly, the NIH-funded team says that the work could pave the way for previously impossible neurodevelopmental studies.’
Organoids occupy a crucial space in research because they can be used to study processes that are difficult to investigate directly at the cellular level in living human brains. However, their typically limited lifespans have largely restricted neuroscientists to studying earlier stages of development. Another challenge has been the high variability between batches of cells, which the researchers addressed by producing cerebral cortex organoids with more consistent cellular compositions.
Consistency was not the team’s only advancement. In laboratory experiments, the organoids also survived and continued developing for much longer periods.
Longer Lifespans
The team tracked biological age and gene expression by observing chemical changes to the genome and examining cellular characteristics down to the level of individual cells. Many key developmental milestones in the organoids, including the emergence and maturation of neurons, occurred on timelines resembling those seen during normal human brain development. The biological clocks in the organoids closely corresponded with the molecular and chronological ages observed in humans.
Although these organoids developed outside the human body, their maturation proceeded at a similarly slow pace.
Notably, neurons in the organoids continued establishing connections and displaying electrical activity for years. The researchers attributed their ability to maintain this activity in part to a specialized fluid designed to support long-term neuronal function.
“The brain doesn’t develop in a vacuum. It’s an organ of incredible complexity that interacts with so many other systems. It was not a given at all that our simplified model would match natural development in this many ways,” said co-first author Irene Faravelli, M.D., Ph.D.
Organoid Neurons
During their experiments, the team transplanted neurons between organoids of different ages to determine how their new environments would affect their development. Remarkably, transplanted neurons largely retained developmental characteristics associated with the organoids from which they originated rather than resetting their developmental trajectories to match their younger surroundings.
“I like to think of this as a sort of ‘warping of developmental time’ indicating that the organoid cells record and recall the time they have already spent in culture. This suggests their development is driven by a cell-intrinsic clock, reflecting mechanisms of endogenous human brain development,” said co-author Paola Arlotta, Ph.D, of Harvard University.
Having significantly expanded researchers’ understanding of what organoids can model, the team now hopes to increase their complexity further, potentially allowing scientists to investigate additional developmental processes and test interventions.
“There is still much to learn about how the embryo naturally builds a progressively more complex and mature brain,” Arlotta concluded. “Applying these lessons to organoids will allow us to model unexplored events of human brain maturation that occur after birth.”
The paper, “Human Brain Organoids Record the Passage of Time over Multiple Years,” appeared in Nature on August 19, 2026.
Ryan Whalen covers science and technology for The Debrief. He holds an MA in History and a Master of Library and Information Science with a certificate in Data Science. He can be contacted at ryan@thedebrief.org.