Human BBB-on-a-Chip using iPSCs Derived HBMECs

Abstract

Blood-Brain Barrier(BBB) is a diffusion barrier protecting our brain and central nervous system (CNS) by blocking the harmful substances crossing from blood to brain. Ironically, the BBB structure becomes a major obstacle for drug delivery to treat brain diseases such as CNS disorders and brain cancers[1]. Therefore, research on effective delivery of drugs across the BBB is of great need. While the in-vivo models can provide the BBB in the physiological environment, its complexity and low throughput hampered in-depth understanding of the BBB function and screening BBB-penetrant drugs. To overcome these problems, the artificial BBB-on-a-chip using microfluidic platform has been proposed. Here, we demonstrate a BBB-on-a-chip using human induced pluripotent stem cells(iPSCs) derived human brain microvascular endothelial cells (HBMECs). The tight junction of human microvascular endothelial cells(HBMECs) is one of the critical cells which form a tight junction in BBB structure[2]. We differentiate HBMECs from iPSCs and co-cultured with human astrocytes and pericytes in a microfluidic chip to achieve a better quality of human BBB-on-a-chip. The Human BBB-on-a-chip consists of the PDMS channels interfaced with PET porous membrane, which allows investigating both apical and basal layers in the BBB system. Overall, this Human BBB-on-a-chip can enhance the function of artificial BBB and potentially useful towards research on drug screening, cancer research, and intracellular communication.