The Center for Alternatives to Animal Testing is an academic center affiliated with the Division of Toxicological Sciences in the Department of Environmental Health Sciences of the Johns Hopkins University Bloomberg School of Public Health.

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Research Grants 2001-2002

Development of an in vitro Cell Model of the Human Blood Brain Barrier

Senén Vilaró, PhD
School of Biology, University of Barcelona, Barcelona, Spain

The development of efficient therapeutic drugs not only requires the optimization of specific and potent pharmacological activity at the target site, but also the efficient delivery of the drug to this site. The main obstacle for efficient drug targeting to the brain lies on the blood-brain barrier (BBB). Separating brain from blood at level of the endothelial cells from cerebral capillaries, this cell barrier strictly controls the concentration and entry of solutes into the central nervous system. To assess the potential toxicity or bioavailability of new drugs in development, academic groups and pharmaceutical companies would benefit from an in vitro model, based on brain endothelial cells in culture, able to mimic the human in vivo BBB. In response to this urgent need and as an alternative method to animal testing, the aim of our proposal is to produce stable, immortalized lines of human brain endothelial cells, which will retain their functional properties, in order to further develop an in vitro cell model of the human BBB for pharmacological and toxicological testing of compounds. Based on the co-culture of astrocytes and immortalized endothelial cells from human brain microvessels, this in vitro cell model will be fully characterized by testing the endothelial cell response to a battery of drugs with known BBB profiles. We are confident that it will represent a valuable alternative to reduce, or even replace, the use of large numbers of animals in drug screening, and will significantly accelerate the CNS-oriented drug discovery and development processes.