National Antivisection Society
New progress made in development of all human tissue model of Blood-Brain Barrier (BBB)
27 May 2009
With 25% of cancers found in the body spreading to the brain and worsening patient prognosis, it is vital to understand the mechanisms by which cancerous cells metastasise (move) into the brain, thereby spreading the cancer. In vitro constructions generally use animal tissues to model the blood-brain barrier (BBB). This is the layer which covers and protects the brain, but these animal models do not reflect the situation in humans.
Exciting new progress has been made in the development of the all human tissue model of the BBB at Portsmouth University. Professor Pilkington and his team have been testing various permutations of cell cultures in the Transwell® model, using astrocytes (supporting cells), from two different areas of the brain, endothelial cells, which line the blood vessels, and pericytes. Pericytes are a less well known component of the BBB and are thought to regulate proliferation and differentiation of endothelial cells.
Recent preliminary results have shown that co-cultures of astrocytes and endothelial cells have shown better formation of ‘tight junctions’ (TJ’s) than endothelial cell mono-cultures. TJ’s make the BBB a highly effective biological barrier to the brain. Currently, the addition of pericytes to create a tri-culture has not improved tight junction formation. However, this is possibly to be due to the pericytes blocking the endothelial cells, preventing them from producing a monolayer. The team intend to repeat the experiment, with the pericytes at the bottom of the Transwell® so that they are not in direct contact with the endothelial cells.
It is hoped the model will identify the pathways malignant cells take to cross the BBB. Once fully developed the model could be used to study metastases and also could be used as a tool by drug companies to discover if and how therapeutic agents can pass through the BBB.
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