Multicellular Integrated Brain Tissue Model for Alzheimer's Disease
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Solution Overview
Problem
Current models fail to accurately recapitulate the complex pathogenesis of Alzheimer's disease, particularly sporadic Alzheimer's, limiting the development of effective therapeutic interventions due to the lack of appropriate in vitro models that mimic human brain physiology and genetics.
Innovation Solution
Development of a 3D multi-cellular integrated human brain model (miBRAIN-chip) comprising a cerebrovascular network with human brain endothelial cells, pericytes, astrocytes, neurons, microglia, and oligodendrocytes, which mimics the human brain's structure and function to assess amyloid plaque development and test therapeutic compounds.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If rodent models are used to study Alzheimer's disease, then research can be conducted with available models, but the models fail to accurately recapitulate human disease pathogenesis and genetic variants
Solution Approach 1:
The patent creates human brain organoids that copy human brain tissue architecture and physiology rather than using rodent models. These organoids are derived from human pluripotent stem cells and recapitulate human-specific genetic variants, proteinopathies, and cellular interactions that rodent models cannot represent, thereby improving both reliability and adaptability to human disease.
Solution Approach 2:
The patent changes the fundamental parameter of species used in modeling from rodent to human. By using human pluripotent stem cells to generate brain organoids, the system maintains human-specific biological parameters including genome sequence, epigenetic regulation, and protein expression patterns that are critical for accurately modeling human Alzheimer's disease pathogenesis.
2Ease of manufacture
If limited human brain tissue accessibility is accepted, then research can proceed with available samples, but the complexity of AD pathogenesis cannot be fully studied
Solution Approach 1:
The patent employs self-organizing properties of human pluripotent stem cells to automatically form complex brain tissue structures with multiple cell types and spatial organization. The organoids self-assemble into functional neural networks that recapitulate human brain architecture without requiring complex external manipulation or limited human tissue samples, thereby improving both accessibility and modeling complexity.
Solution Approach 2:
The patent segments the complex task of modeling entire human brain pathology into manageable organoid units that can be independently generated, analyzed, and manipulated. Each organoid contains representative cellular compositions and pathological features that can be studied in isolation while maintaining the ability to model complex disease processes through controlled experimental conditions.
3Ease of operation
If simple cell cultures are used, then experimental simplicity is maintained, but the multi-faceted proteinopathies and vascular pathology cannot be captured
Solution Approach 1:
The patent creates composite brain organoid systems that integrate multiple cell types (neurons, astrocytes, microglia, oligodendrocytes) and functional components (vascular networks, blood-brain barrier) within a single three-dimensional structure. This composite approach maintains relative experimental simplicity while capturing the complex multi-faceted proteinopathies and vascular pathologies characteristic of Alzheimer's disease through the natural interactions of diverse cellular components.
Data Source
AI summary
The present disclosure provides, in some embodiments, in vitro brain (miBRAIN) having functional and structural properties of in vivo brain as well as methods of identifying compounds capable of influencing brain function.