M105:Blood-Brain Barrier and Brain Vessel Formation Using a Microfluidic Platform
Authors: Ju Hun Yeon, Qing Ping Hu, Hyun Ryul Ryu, Min Hwan Chung and Noo Li Jeon
Affiliation: School of Mechanical and Aerospace Engineering, Seoul National University, Korea
Human brain is composed by a variety of cells which are specialized types of neurons, endothelial cells, astrocytes and
pericytes with interconnected cellular interactions. Especially, drug transport from blood vessel to brain is restricted by
specialized membrane of brain capillary endothelial walls, named blood brain barrier (BBB), which is a unique biological
structure composed of capillary endothelial cells, basal lamina and astrocytes.
For studying BBB and brain vessel formation, various in vivo and in vitro models have been developed. In vivo models, the
observation of angiogenesis is technically difficult and observed effects are also difficult to quantify. For this reason, the
compound screening for angiogenesis on in vivo models was limited and the development of angiogenesis research was
restrained. Recently, several in vitro models have been attempted to recreate the complex sequence of events of
angiogenesis with varying degrees of success. However, the formation of new blood vessels and blood vessel fusion were not
attempted to study in vitro models because it was not proved the appropriate model for angiogenesis and vascular fusion.
Moreover, it was not possible to screen the drugs which affect to angiogenesis and vessel formation because the formation of
new vessels and the process of vessel fusion were random.
In this study, we developed a novel microfluidic device using the appropriate micro-architecture and 3D hydrogel for
mimicking brain vessel and BBB. Using 3D hydrogel, we made the 3D structure for the formation of brain vessel and attached
endothelial cells on the wall of 3D hydrogel. After co-culturing of endothelial cells and fibroblast in the 3D hydrogel, we
observed the formation of brain vessel and BBB by the specific staining the tight junction among endothelial cells. This device
demonstrates its capability to precise control the cellular environment, the direction of vessel growth and the distribution of
new vessels. Furthermore, using this microfluidic device, it is possible to select and screen the useful drugs for brain vessel
angiogenesis and vascular fusion. For drug screening through brain vessel, it will be a useful tool and a new method reflecting
the in vivo-like environment and it will be beneficial to quantitative drug-related assay in further research.