Human blood-brain barrier
Protecting the brain – the neurovascular unit
The human brain is arguably the most delicate system in our body. Therefore, a protective blood-brain barrier (BBB) restricts passive diffusion of large polar substances and potentially neurotoxic compounds from the circulation into the brain. In addition, specialized transporters make sure the brain receives the required nutrients and can get rid of metabolic toxins and waste products.
The brain’s blood vessels are formed by highly specialized brain microvascular endothelial cells. Other cells surrounding the vasculature, including astrocytes and pericytes, also contribute to the development and maintenance of the blood-brain barrier and together these cells form the neurovascular unit (NVU).
The need for better predictive models
Blood-brain barrier dysfunction is seen in almost all disorders of the central nervous system (CNS) and disease severity is often correlated to the extent of BBB disruption. Therefore, understanding BBB breakdown is essential to a wide spectrum of CNS disorders. Moreover, many drugs that target CNS disorders are unable to cross the blood-brain barrier and enter the brain. A new in vitro model that closely mimics the in vivo BBB can help study blood-brain barrier integrity in healthy and diseased tissue as well as contribute to proper selection of drug candidates and study their entrance into the brain. To enable this, MIMETAS will develop an in vitro model in the OrganoPlate comprising a microvessel of brain endothelial cells enwrapped with pericytes and astrocytes as well as CNS neurons to fully model the human neurovascular unit.
Figure: In vitro BBB model comprising a microvessel of endothelial cells in direct contact with astrocytes. Human astrocytes (green) were taken up in ECM gel and seeded in the gel channel of the OrganoPlate. After gelation, human umbilical vein endothelial cells (HUVECs, red) were seeded in the adjacent medium channel and perfusion was started to enable the formation of a microvessel.