3D Blood-Brain Barrier Model With Human Neurovascular Co-Culture
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Solution Overview
Problem
Current in vitro blood brain barrier models lack physiological relevance, failing to accurately represent both the physical and metabolic states of the blood brain barrier, often using non-human cells and focusing only on the physical barrier rather than the metabolic barrier comprised of the functional neurovascular unit.
Innovation Solution
A 3D in vitro model incorporating a cell population of endothelial cells, astrocytes, and pericytes within a 3D cell growth material, cultured under shear stress to achieve a TEER value of at least 450 Ω/cm², mimicking the in vivo blood brain barrier's physical and metabolic properties.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If traditional in vitro blood brain barrier models are used, then the model structure is simple and easy to manufacture, but the model lacks comprehensive representation of both physical and metabolic states
Solution Approach 1:
The patent combines multiple cell types (endothelial cells, astrocytes, pericytes) and functional components (physical barrier, metabolic enzymes, transporters) into a single integrated 3D co-culture model. This merging of previously separate model components creates a comprehensive system that simultaneously represents both physical and metabolic states of the blood-brain barrier, resolving the contradiction between model simplicity and physiological relevance.
Solution Approach 2:
The patent transitions from traditional 2D monolayer models to a three-dimensional co-culture system. This dimensional change enables more realistic cell-cell and cell-matrix interactions, allowing the model to better represent the complex physiological environment of the blood-brain barrier while maintaining a manageable experimental structure.
2Reliability
If non-human cells are used in the model, then the model is easier to establish, but the model lacks species-specific relevance for in vitro-in vivo correlations
Solution Approach 1:
The patent changes the key parameter of cell species from non-human to human cell lines. This parameter change ensures species-specific relevance for predicting human drug behavior and improves in vitro-in vivo correlation. The use of human endothelial cells, astrocytes, and pericytes allows the model to accurately reflect human blood-brain barrier physiology, metabolism, and transporter function.
3Reliability
If the model focuses only on the physical barrier, then the model is simpler to construct, but the model fails to represent the metabolic barrier function
Solution Approach 1:
The patent creates a multi-functional model that simultaneously performs physical barrier function, metabolic processing, and transporter-mediated selective permeability. The inclusion of astrocytes and pericytes alongside endothelial cells enables the model to execute multiple barrier functions concurrently, making it a universal platform for studying both physical and metabolic aspects of blood-brain barrier regulation.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The model provides a more accurate reflection of the in vivo blood brain barrier, enhancing in vitro-in vivo predictions of molecule permeability, particularly for drug development, by maintaining high transendothelial resistance and metabolic activity.
Implementation Method 1
a 3D (three dimensional) cell growth material within which the cell population is located
Implementation Method 2
the structure separates a first chamber located on a first side of the structure and a second chamber located on a second side of the structure
Data Source
AI summary
Provided is a structure composed of a cell population comprising endothelial cells, astrocytes and pericytes, and a 3D (three dimensional) cell growth material within which the cell population is located. The structure has a TEER value of at least 450 Ω/cm2. The cells of the structure may be derived from the brain. The cells may be human cells, and in particular may be primary derived non-immortalised cells. The structure is particularly suited for use in a model of the blood brain barrier, and the invention also provides such a model. The structure is located in a container, in which it separates a first chamber located on a first side of the structure and a second chamber located on a second side of the structure. The first and second chambers respectively contain first and second liquids in contact with first and second sides of the structure. The liquids mimic the brain extracellular fluid and the blood. The blood brain barrier model provided may be used in models of brain disease, and to investigate uptake of agents into the brain or diseased brain.