Scientists at Johns Hopkins University have created a lab-grown “whole-brain” organoid, an amazingly complex mini-brain that can reshape how we study schizophrenia, autism, Alzheimer’s and other whole-brain neurological disorders.
Unlike earlier models that replicate only one region, this new multi-regional brain organ (MRBO) includes signs of connected tissue from the entire brain, basic blood vessels, and even blood-brain barriers. It was a leap in modeling the development, failures and responses to treatments of the human brain, never entering the human skull.
Brain in the disk, reintegrating realism
“We have become the organs of the next generation of brains,” said Annie Kathuria, the principal author of the study and assistant professor of biomedical engineering at Johns Hopkins. “Most of the brain organs you see in the paper are a brain region, such as the cortex or the hindbrain or the midbrain. We have grown a basic whole-brain organ; we call it the multi-regional brain animal (MRBO).
Achievements published in Advanced Sciencemarking the first successful integration of brain, mid/hindbrain and vascular components into a single organ. The resulting structure reflects approximately 80% of the cell types found in the brain of a 40-day-old human fetus, including neural progenitors, mature neurons, pericytes and endothelial cells.
How to grow the brain
To construct MRBO, Kathuria’s team grew organs and vascular tissues in a single brain region separately from human-induced pluripotent stem cells. Then use a sticky protein and a matrix to fuse them together to form a whole. As they mature, the tissues begin to communicate electrically, similar to coordinated brain activity.
In fact, they assembled a working brain-like structure from scratch and had signs of electrostrophobia, regional patterns, and even early blood-brain barrier formation.
Why it matters: Diseases that don’t stay in one area
Neurological diseases such as autism and schizophrenia are not limited to part of the brain. Traditional models, often limited to animal brains or isolated brain regions, cannot capture this complexity. MRBO may change that.
- MRBO replicates nerve and blood vessel interactions in the brain, midbrain and hindbrain regions.
- Organs show the development of the blood-brain barrier, a key interface for many neurological diseases.
- Electrophysiological tests reveal complex patterns of network activity between brain regions.
- Endothelial cells affect hindbrain development, but not brain regions, suggesting region dependence.
- During the Carnegie phase, the gene expression pattern matches 80% of the cells in the human fetal brain.
“If you want to understand neurodevelopmental disorders or neuropsychiatric disorders, we need to study models of human cells,” Kathuria explained. “But I can’t ask someone to let me peek at their brains just to learn about autism.”
One brain, many possibilities
The MRBO model opens new avenues for testing drug effects in human-like systems, especially since in early trials, more than 90% of neuropsychiatric drugs failed. With the ability to observe the disease unfolds in real time, researchers can eventually use patient-specific organoids to tailor treatment strategies, especially for complex cross-regional diseases such as bipolar disorder or vascular dementia.
“The whole brain organ allows us to observe the disease progresses in real time to see if the treatment is effective, and even tailor therapies to individual patients,” said Catheria.
Future instructions and warnings
Although the organoid has not replicated long-distance brain wiring or fully functional blood-brain barrier, it is closer than previous models. Ongoing work is designed to incorporate microglia and other immune cells to increase realism. In the future, MRBO may help bridge the gap between basic laboratory research and clinical trials.
For now, this lab’s mini-brain hasn’t thought, felt or dreamed yet. But this is a response. This may change the way we respond to some of the brain’s most mixed diseases.
Journal Reference
title: Multi-regional brain organs integrate brain, mid-rear brain and endothelial system
author: Anannya Kshirsagar, Hayk Mnatsakanyan, Sai Kulkarni, John Guo, Kai Cheng, Kai Cheng, Luke Daniel ofria, Oce Bohra, Ram Sagar, Ram Sagar, Vasiliki Mahairaki, Christian E Badr, Annie Kathuria, Annie Kathuria
Magazine: Advanced Science
doi: 10.1002/advs.202503768
release: July 8, 2025
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