Researchers at the Massachusetts Institute of Technology (MIT) have made a significant advancement in neuroscience with the development of a new 3D brain tissue model, known as Multicellular Integrated Brains or miBrains. This innovative platform, created from patient-specific stem cells, allows scientists to grow individualized human brain models that can be used to study neurological diseases and test new therapies.
The miBrains replicate essential features of authentic human brain tissue, offering a more precise method for drug testing and understanding disorders such as Alzheimer’s. This breakthrough emerges as neuroscience shifts towards systems that more accurately reflect human brain functions, moving away from traditional laboratory and animal models.
Combining Strengths of Existing Models
Each miBrain is smaller than a dime yet integrates the six primary cell types found in the human brain, including neurons, glial cells, and vascular structures. According to Li-Huei Tsai, director of The Picower Institute for Learning and Memory at MIT, “The miBrain is the only in vitro system that contains all six major cell types that are present in the human brain.”
Traditional approaches in brain research typically rely on simplified cell cultures or animal models. While cell cultures are straightforward to produce, they lack the intricate complexity required to study the interactions among different brain cells. Conversely, animal models provide a more complete biological context but are costly, slow, and sometimes unreliable in predicting human outcomes.
The miBrains effectively combine the advantages of both methods. They are not only easy to cultivate and modify but also complex enough to emulate real brain behavior. Because the models are derived from patient-specific stem cells, researchers can create personalized versions that reflect an individual’s genetic makeup.
Insights into Alzheimer’s Disease
In their initial demonstration, researchers utilized miBrains to investigate how the APOE4 gene variant, which is the strongest genetic predictor of Alzheimer’s disease, influences cell interactions leading to disease-related changes. The study indicated that astrocytes carrying the APOE4 variant triggered immune reactions similar to those observed in Alzheimer’s, but only when integrated into the multicellular miBrain environment.
The research team discovered that these APOE4 astrocytes facilitated the accumulation of amyloid and tau proteins linked to Alzheimer’s. This accumulation depended on the interaction with microglia, the brain’s immune cells. Such findings underscore the potential of miBrains to reveal disease mechanisms that simpler models might overlook.
The development of these models took years of rigorous experimentation, particularly in engineering a structure that could support multiple cell types while ensuring their viability. The research team designed a hydrogel-based “neuromatrix” that replicates the brain’s natural environment using a composite of polysaccharides, proteoglycans, and other molecules that promote functional neuron development.
Robert Langer, co-senior author of the study, noted that “recent trends toward minimizing the use of animal models in drug development could make systems like this one increasingly important tools for discovering and developing new human drug targets.”
The researchers plan to enhance the miBrains by integrating features such as microfluidic blood flow and advanced single-cell profiling, making these systems even more lifelike.
“I’m most excited by the possibility to create individualized miBrains for different individuals,” Tsai added. “This promises to pave the way for developing personalized medicine.”
The study detailing this groundbreaking work is published in the Proceedings of the National Academy of Sciences, marking a significant step forward in the quest for tailored therapies in neurological conditions.
