Multicellular Integrated Brain Tissue for Investigation and Therapeutic Discovery in Neurological Diseases

Technology 

The miBRAIN is formed through a tissue-engineering approach that harnesses the innate ability of different brain cell types to self-assemble into a functional 3D structure. The in vitro blood-brain barrier (iBBB) is constructed by incorporating brain endothelial cells, astrocytes, and pericytes into a matrix that promotes cellular interactions and self-assembly. Neurons, oligodendrocytes, and microglial cells are then added to complete the brain-like tissue. To achieve this assembly, the inventors established common media and growth conditions to sustain all six cell types, defined precise cell ratios and densities to reflect native brain composition, and selected extracellular matrix scaffolding that mimics the brain’s physical and biochemical environment. The miBRAIN can be used for therapeutic screening by measuring how candidate compounds influence outcomes such as amyloid-beta production. Additionally, by differentiating the mature brain cell types from a patient-derived iPSC, the miBRAIN can be used to model individual genetic profiles for personalized testing.  

Problem Addressed 

Alzheimer’s disease (AD) affects millions in the US and remains without effective treatments, largely due to its complex and poorly understood pathology. The causes of sporadic AD, which accounts for more than 95% of all AD cases, remain largely unknown. Even well-established genetic risk factors like APOE4 lack clearly defined mechanisms that could guide the development of effective treatment strategies. Furthermore, animal models often fail to replicate key aspects of human brain biology, resulting in the failure of promising drug candidates during late-stage clinical trials. To address this challenge, the researchers have developed a human cellular model system that recapitulates phenotypic, mechanistic, and pathological features of AD and related dementias. This system supports biomarker discovery, mechanistic studies, and therapeutic screening in a physiologically relevant human context.  

Advantages 

• Human cell-based model incorporating six major brain cell types, including a functioning blood-brain barrier 

• Allows for direct assessment of amyloid plaque development and therapeutic efficacy 

• Supports high-throughput drug screening in a physiologically relevant human brain environment 

• Supports personalized modeling using patient-derived iPSCs