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A Quasi-Physiological Microfluidic Blood-Brain Barrier Model for Brain Permeability Studies
Behnam Noorani1,2, Aditya Bhalerao3, Snehal Raut4
1Department of Pharmaceutical Sciences, Jerry H. Hodge School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, TX 79106, USA.
Pharmaceutics
|September 28, 2021
Summary
A new microfluidic organ-on-a-chip model accurately mimics the human blood-brain barrier (BBB). This advanced in-vitro model uses stem cells and co-cultures for highly predictive drug development.
Area of Science:
- Biomedical Engineering
- Neuroscience
- Cell Biology
Background:
- Conventional 2D models fail to replicate the complex microvasculature of the brain.
- Organ-on-a-chip technology offers a more physiologically relevant in-vitro system.
- Developing accurate blood-brain barrier (BBB) models is crucial for neurological drug discovery.
Purpose of the Study:
- To develop and validate a novel microfluidic blood-brain barrier (BBB) model.
- To create an in-vitro system that recapitulates in situ BBB hemodynamic and architectural features.
- To establish a highly predictive and translationally relevant BBB model for research.
Main Methods:
- Utilized induced pluripotent stem cell (iPSC)-derived brain microvascular endothelial cells (BMECs) in co-culture with primary human pericytes and astrocytes.
- Employed a microfluidic platform to mimic brain microvasculature.
- Quantified permeability coefficients of [13C12] sucrose and [13C6] mannitol using LC-MS/MS.
Main Results:
- The microfluidic BBB model exhibited continuous tight-junction patterns and low permeability to sucrose and mannitol.
- Demonstrated quasi-physiological responses to hyperosmolar conditions and p-glycoprotein inhibitor treatment.
- Confirmed long-term viability and BBB integrity through astrocyte and pericyte co-culture.
Conclusions:
- The novel multi-culture microfluidic platform successfully replicates a quasi-physiological brain microvasculature.
- This advanced organ-on-a-chip model enables the development of more predictive in-vitro BBB studies.
- The platform supports translationally relevant research for neurological diseases and drug development.
