Introduction to the Blood-Brain Barrier
TThe blood-brain barrier (BBB) explains why certain substances circulating in the blood are able to get into the brain and others do not. The BBB is formed by brain capillaries that look like simple tubes of endothelial cells. Experimental and clinical evidence suggests that the BBB maintains the chemical environment for neuronal function and protects the brain from harmful substances. The blood-brain barrier is therefore crucial for complex issues such as drug delivery, pathogenesis of chronic neurological diseases, and issues related to bio-defense. We have developed a practical in vitro model that accurately reflects BBB characteristics.
Benefits of Flocel’s in vitro BBB Model
In contrast to other available models of the blood-brain barrier, Flocel's Dynamic In vitro Blood-Brain Barrier (DIV-BBB) respects the anatomical aspects of the in situ endothelial cell-astrocyte interactions and replicates the physiological levels of shear stress to which in situ endothelial cells are exposed. The DIV-BBB allows formation of physiological transendothelial resistance, and formation of gap junctions that can be easily visualized at the electron microscope or determined experimentally with the use of tracers.
Mission
Flocel Inc. is a biotechnology company dedicated to innovation towards helping the research community better conduct and advance in vitro studies.
Current Projects
A new dynamic In vitro modular capillaries-venules modular system: Cerebrovascular physiology in a box
A new dynamic In vitro modular capillaries-venules modular system: Cerebrovascular physiology in a box
The study of the cerebrovascular physiology is crucial to understand the pathogenesis of neurological disease and the pharmacokinetic of drugs. Appropriate models in vitro often come short in representing in vivo physiology. Essential for the resolution of this problem is a novel artificial vascular system that closely mimics the multiple segments of human cerebrovascular network and allows for an extensive control of the experimental variables and their manipulation. The unique characteristics afforded by the DIV-BBB in combination with a venule segment will realistically expand our ability to dissect and study the physiological and functional behavior of distinct segments of the human cerebrovascular network. This novel tool will provide a valuable instrument to facilitate the discovery of novel therapeutic strategies aimed at brain targets to reduce the burden of neurological disorders.
The DIV-BBB predicts CNS drug toxicity
The DIV-BBB predicts CNS drug toxicity
Drugs and their metabolites often produce undesirable effects. This may be due to a number of mechanisms including biotransformation by P450 enzymes. These are not exclusively endowed in hepatocytes since functional expression of metabolic enzymes was found at the drug resistant epileptic blood-brain barrier. The possibility thus exists that the potency of central nervous system therapeutics can be neutralized by a metabolic blood-brain barrier. Furthermore, metabolism of neurotherapeutics may lead to production of toxic compounds. Our published work demonstrates that the Flocel apparatus can predict how the blood-brain barrier transforms a given drug into potentially harmful metabolites.
Human Glioma Stem Cells
Human Glioma Stem Cells
Improved culture and condition allow survival of stem cells. Cells were isolated from a primary brain tumor (glioblastoma) and cultured for 1 week. The media used were identical in both experiments. The main difference consisted in a different metabolic utilization of glucose and oxygen in cells cultured under dynamic conditions.
Growing BBB cells under dynamic conditions mimic brain inflammation
Growing BBB cells under dynamic conditions mimic brain inflammation
Cells were grown as recommended to achieve a viable BBB; at that time white blood cells were isolated from a human donor and perfused in lumen of the system. A brief episode of no perfusion disrupted the barrier. However, when white blood cells were pre-treated with Ibuprofen this effect was greatly reduced.
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