Scientists at the Massachusetts Institute of Technology (MIT) have unveiled a pioneering 3D brain tissue model, known as Multicellular Integrated Brains, or miBrains. This innovative technology uses patient-derived stem cells to create personalized human brain models, enabling researchers to study neurological diseases and evaluate new therapies more effectively.
The miBrains mimic critical features of actual human brain tissue, providing a more reliable platform for testing drugs and understanding conditions such as Alzheimer’s disease. This advancement comes at a crucial time when neuroscience is evolving beyond traditional lab models and animal testing, striving for systems that accurately reflect human brain functionality.
Combining the Best of Both Worlds
Each miBrain, roughly the size of a dime, integrates six major brain cell types, including neurons, glial cells, and vascular structures, into a single living model. According to Li-Huei Tsai, the Picower Professor and director of The Picower Institute for Learning and Memory, “The miBrain is the only in vitro system that contains all six major cell types that are present in the human brain.”
Researchers demonstrated the model’s capabilities by investigating the effects of a common genetic marker for Alzheimer’s disease. The findings revealed how this marker influences cell interactions, leading to changes associated with the disease.
Traditional methods in brain research primarily rely on two approaches: simplified cell cultures and animal models. While cell cultures offer ease of production, they lack the necessary complexity to study intricate cell interactions. Conversely, animal models provide biological completeness but are often costly, slow, and sometimes unreliable in predicting human outcomes.
By bringing together the strengths of both systems, miBrains present a versatile alternative. They are not only simple to cultivate and modify but also complex enough to replicate genuine brain behavior. Derived from patient-specific stem cells, these models can reflect an individual’s unique genetic profile.
Innovative Engineering for Realistic Models
The creation of a model encompassing multiple cell types required extensive experimentation. One significant challenge was developing a framework that could support the cells and maintain their activity. The team crafted a hydrogel-based “neuromatrix,” which simulates the brain’s natural environment using a combination of polysaccharides, proteoglycans, and other molecules to encourage functional neuron development.
To establish realistic brain tissue, researchers generated six types of brain cells from donor stem cells, carefully adjusting their proportions until they formed operational neurovascular units. This modular design allows for precise control over cellular inputs and genetic backgrounds, making the miBrain an invaluable tool for disease modeling and drug testing. Lead author Alice Stanton emphasized the model’s adaptability, stating, “Its highly modular design sets the miBrain apart, offering precise control over cellular inputs, genetic backgrounds, and sensors.”
In their initial testing, researchers focused on the APOE4 gene variant, the most significant genetic risk factor for Alzheimer’s disease. They found that astrocytes with the APOE4 variant triggered immune responses associated with Alzheimer’s only when integrated into the miBrain environment. Additionally, these astrocytes promoted the accumulation of amyloid and tau proteins linked to the disease, with their effects dependent on interactions with microglia, the brain’s immune cells.
These insights underscore the potential of miBrains to uncover disease mechanisms that simpler models might overlook. The research team aims to enhance the system further by incorporating features such as microfluidic blood flow and advanced single-cell profiling, striving to make the model even more lifelike.
“I’m most excited by the possibility to create individualized miBrains for different individuals,” Tsai remarked. “This promises to pave the way for developing personalized medicine.”
The comprehensive study detailing these findings has been published in the journal Proceedings of the National Academy of Sciences. This groundbreaking approach not only marks a significant milestone in brain research but also offers a promising avenue for future therapies tailored to individual patients.
