Here’s what you’ll learn when you read this story:
In recent years, organoids—self-assembling cells developed from stem cells—have provided scientists ways to investigate diseases and disorders in the lab without the need for animal models or donated human organs.
Scientists from Johns Hopkins University have created what they call the “next generation of brain organoids” which connect different regions of the brain into one whole-brain organoid.
Scientists hope to use this breakthrough to increase the speed and efficiency of drug trials for nueropsychiatric disorders.
Over the years, scientists have gotten increasingly more proficient at creating in vitro organoids—self-assembling, 3D cultures derived from stem cells that mimic certain organs of the brain—in an attempt to better understand these organs and the diseases and disorders that impact them. In 2022, scientists created DishBrain, an assembly of 800,000 neurons that was capable of playing the video game Pong (three years later, the company Cortical Labs released the CL-1, a computer than runs on human brain cells). Some scientists even think these organoids could display some level of consciousness.
Now, scientists at Johns Hopkins University (JHU) have developed what they describe as the “next generation of brain organoids.” Instead of mimicking one region of the brain, the research team instead developed a “whole brain” organoid with various regions acting in concert with one another. The researchers call this breakthrough a “multi-region brain organoid,” or MRBO, and detail how they constructed this new kind of organoid in a study published in the journal Advanced Science.
“We need to study models with human cells if you want to understand neurodevelopmental disorders or neuropsychiatric disorders, but I can’t ask a person to let me take a peek at their brain just to study autism,” Annie Kathuria, senior author of the study from JHU, said in a press statement. “Whole-brain organoids let us watch disorders develop in real time, see if treatments work, and even tailor therapies to individual patients.”
To create this new kind of mini-brain, Kathuria and her team first grew neural cells for differing regions of the brain, along with rudimentary blood vessels (grown in separate petri dishes). Then, the scientists combined those different parts with a sticky protein that acted as a kind of “biological superglue,” according to the press statement. This protein-based scaffolding allowed tissues to form connections and (eventually) electrical networks.
The resulting MRBO is far removed from a fully-formed human brain, containing only 6 to 7 million neurons instead of the tens of billions found in a typical human brain. The scientists estimate that their MRBO closely mimics the brain formation of a 40-day-old fetus, and in a fascinating twist, the researchers also saw the early formation of the blood-brain barrier—a gatekeeping layer of cells that controls what microbes and nutrients can access the brain—within the MRBO.
“This is the new generation of brain organoids, which is a great improvement to the modeling of brain development and the pathophysiology of the fetal brain,” the authors write. “With three main regions of the brain and the endothelial system, the MRBOs allow the analysis of highly complex human brain function over time.”
The creation of MRBOs isn’t to design some sort of next-gen neuromorphic computer, but to improve the success rate of drug trials. Because scientists often rely on animal models for testing drugs during Phase 1 trials, results don’t always translate perfectly to humans. Having a reliable platform that more closely mimics the human brain in miniature will hopefully make drug development faster and more efficient.
“Diseases such as schizophrenia, autism, and Alzheimer’s affect the whole brain, not just one part of the brain,” Kathuria said in a press statement. “If you can understand what goes wrong early in development, we may be able to find new targets for drug screening.”
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