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P23 A three dimensional (3D) human in vitro blood-brain barrier (BBB)
  1. P Miranda Azpiazu,
  2. S Panagiotou,
  3. G Jose,
  4. S Saha
  1. Division of Cardiovascular and Diabetes Research, Leeds Institute of Cardiovascular and Metabolic Medicine (LICAMM), University of Leeds, Leeds, UK

Abstract

Rationale The blood-brain barrier (BBB) is the crucial frontier between the blood and the brain. It has been suggested a relationship between diabetes or stroke and a loss of BBB integrity, although the mechanisms of these BBB changes still unknown. This study aims to develop a novel in vitro BBB model to further investigate the function of the BBB in health and disease.

Methodology The three main human primary cell types involved in BBB formation (endothelial cells, astrocytes and pericytes) were co-cultured using Kirkstall Quasi Vivo system. Tightness of the BBB and permeability were carried out by measuring both transendothelial resistance (TEER) and passage of sodium fluorescein and different molecular weight dextrans, respectively. Single and double Immunohistochemical localization of these tight junctions (zonula occludens, ZO1 and occludin) was also studied to prove the quality of the barrier.

Results High TEER values were obtained and permeability of compounds was reduced when compared to control (without cells).

Conclusion This system will allow us to explore specific interactions between the brain endothelial cells, astrocytes and pericytes that may regulate BBB morphology and function. Success of this model could lead to the development of new therapies for vascular and brain diseases

We would like to acknowledge the support received by Innovate UK and the Biotechnology and Biological Sciences Research Council (BBRSC), as well as the collaboration of Kirkstall Ltd.

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