The more closely a model recapitulates the brain’s complexity, the better suited it is for extrapolating how human biology works and how potential therapies may affect patients. In the brain, neurons interact with each other and with various helper cells, all of which are arranged in a three-dimensional tissue environment that includes blood vessels and other components. All of these interactions are necessary for health, and any of them can contribute to disease. Yet for obvious ethical reasons, one cannot typically experiment on an actual living human brain. 

That’s why MIT scientists and engineers led by Professors Li-Huei Tsai, Robert Langer, and Joel Blanchard teamed up to develop the multicellular integrated brain, “or miBrain,” the first 3D human brain tissue culture that integrates all six major cell types: neurons, astrocytes, microglia, oligodendrocytes, pericytes and endothelial cells. Embedded in an ingenious hydrogel, the cultures self-assemble into functioning units, including blood vessels with working blood-brain barriers, immune defenses, myelinated neurons and neural signal conduction, among other features.

In a miBrain, each cell type is derived from an individual donor’s skin cells. The donated cells are induced to become stem cells and then those are differentiated into brain cells. As such, a miBrain carries the genome of the donor, making it a personalized brain tissue model. The genome can be edited in the culture, enabling “isogenic” comparisons of the effects of different gene versions. For instance, in the 2025 paper in PNAS that introduced the miBrain, the research team led by former postdocs Alice Stanton and Adele Bubnys, used miBrain to compare the effects of the APOE4 and APOE3 gene variants on Alzheimer’s pathology.

miBrains are also well suited to enable personalized testing of drug delivery and candidate therapeutics. For example, the labs have demonstrated the ability to develop fully working circulatory systems within the miBrains. In a 2025 preprint study they achieved perfusion by hooking the miBrains up to a microfluidic system.