Scientists’ ability to recapitulate the human brain in a dish has always been hindered by the inability to model the full capacity of the brain and its development through time.
In a new study published Aug. 19 in Nature, researchers from Harvard University show that a brain organoid, derived from a vial of blood, is able to record the passage of time and remain alive in a dish for five years.
Over the five years that these brain organoids were kept alive, they tracked the transcriptional and epigenomic changes through time and found that the organoid developed cells and aged over the years consistent with human brain development after birth.
“For biomedicine, we might see a renaissance of new therapies that will emerge, where for decades and decades, nothing worked.” Paola Arlotta, Ph.D., professor of stem cell and regenerative biology at Harvard University and corresponding author, told Fierce. “This system is an approach and a pipeline that must be used in the context of biotech, startups and industry. It has demonstrated to be able to do some powerful things that no other model in the past [could do]. It is a link to patients.”
In this study, researchers started with a vial of blood from a blood draw, extracted stem cells from the blood, and grew these cells until they were mature enough to be turned into an organoid that modeled the cerebral cortex during development. Over time, they maintained the cells in a dish by altering the mix of nutrients that were given to the cells to promote their survival and development.
One unique aspect of the organoids was that they developed excitatory neurons, or cells that can send electrical signals to nearby and distant brain areas. These cells are essential for higher thinking processes in the brain, such as learning, memory, sensory perception and motor control.
Organoids are 3D balls of cells that are notoriously tricky to grow in a dish—they are needy, picky when it comes to the nutrients they receive, and usually only last a few weeks to months in culture, Arlotta noted. Her team has been looking to test the boundaries of how far organoids can go to measure early human developmental stages.
“This work sits in the broader field of how organoids are going to help the understanding of mechanisms of disease, the development of new pipelines for developing more effective therapeutics,” Arlotta said. “I think we are at a moment in time when organoids recapitulate with fidelity and reproducibility enough of the biology of the endogenous brain.”
Arlotta described these brain organoids as “brain avatars”, as they are a “reductionist replica of the tissue of a patient” that can be used in the lab to make predictions about what a patient’s brain may do.
“If you had brain avatars that were generated from a patient with a disease, and they showed you a fingerprint of disease—gene expression profiles that would be different or electrophysiological properties that would be different from that of an isogenic control or a control in general without the disease—given that you can make [thousands] of these organoids in a platform.”
Organoids have become a hot topic to study, particularly for the brain, as it is a well-protected and complex organ in our body. Scientists are still trying to crack the code of how to model the brain in its entirety in a dish but have made strides to use organoids to study traumatic brain injury and autism.
In April 2025, the FDA published a roadmap to prioritize new approach methodologies (NAMs) in research, such as artificial intelligence, machine learning and organoids. This push came with the goal of reducing animal testing in preclinical research, expediting drugs to market, and improving predictive accuracy in drug testing.