Can you guess what the tiny white balls are in this photo? Here’s a hint: they represent the organ you’re using to answer this question.
These are 3D brain organoids grown from human pluripotent stem cells in a culture dish. They act as miniature models of the human brain, containing many of its cell types, structures, and regions.
Scientists use brain organoids to study how the human nervous system develops and to model neurological and psychiatric disorders. These models let researchers investigate the brain’s inner workings—something they can’t do in living patients.
Brain-in-a-Dish
Dr. Sergiu Pasca, a Stanford University professor, uses 3D cultures to study human brain development. His lab has developed methods to create different types of brain organoids from induced pluripotent stem cells (iPSCs), allowing researchers to mimic key stages of human brain development in a dish.
My colleague, Todd Dubnicoff, blogged about Pasca’s research last year:
“Using brain tissue grown from patient‑derived iPSCs, Dr. Sergiu Pasca and his team recreated the nerve cell circuits that form late in pregnancy in the fetal cerebral cortex—the brain’s outer layer responsible for memory, language, and emotion. With this system, they observed abnormalities in how these circuits assemble, offering new insights into the cellular and molecular causes of neuropsychiatric disorders such as autism.”
Brain Organoids
Pasca created brain organoids from the iPSCs of patients with Timothy Syndrome, a genetic disease that causes heart problems and some autism‑related symptoms. When he compared patient‑derived organoids with healthy ones, he saw disrupted nerve cell migration in the Timothy Syndrome models.
“We’ve never been able to recreate these human‑brain developmental events in a dish before,” Pasca said in a press release. “The process happens in the second half of pregnancy, so watching it live is difficult. Our method lets us see the entire movie, not just snapshots.”
The Rise of 3D Brain Cultures
Pasca’s lab is one of many using 3D brain culture technologies to study human development and disease. These tools are becoming popular because they let scientists examine human brain tissue in both normal and abnormal conditions. Brain organoids have also appeared in mainstream news as new ways to study how epidemics like the Zika virus affect the developing fetal brain.
These advances are exciting, but the field is still young, and 3D organoid models cannot yet fully represent the complexity of the human brain.
Pasca reviews the progress and challenges of 3D brain cultures in an article titled “The rise of three-dimensional brain cultures,” published this week in Nature. He describes how pluripotent stem cells can assemble into structures that mimic different brain regions, allowing scientists to observe how cells interact within neural circuits and how disease disrupts these circuits.
Brain organoids for screening drugs
Brain organoids are also being used to screen for new drugs and to model complex diseases like Alzheimer’s.
Human pluripotent stem cells, adult stem cells, or cancer cells can generate microfluidics‑based organs‑on‑a‑chip (top), undirected organoids (middle), and region‑specific brain organoids or spheroids (bottom). Scientists can edit these 3D cultures with CRISPR‑Cas9, transplant them into animals, or use them for drug screening. (Pasca, Nature)
Pasca ends the review by outlining the major challenges facing 3D brain culture technologies. He notes that these cultures only approximate real neural tissue and that the cells and structures inside organoids can be unpredictable. Over time, researchers can address these issues by improving quality control and using new biomaterials that support organoid growth and maturation.
Still, Pasca argues that 3D brain cultures, combined with advancing analytical tools, “have the potential to give rise to novel features for studying human brain development and disease.”
He closes with a cautiously optimistic outlook:
“This is an exciting new field, and like many technologies, it may follow a ‘hype’ cycle in which we overestimate its effects in the short run and underestimate its effects in the long run. A better understanding of this platform’s complexity, along with interdisciplinary approaches, will help move us up the ‘slope of enlightenment’ and into the ‘plateau of productivity’.”
