Publication date: Jun 06, 2019
The blood-brain barrier (BBB) tightly regulates the entry of solutes from blood into the brain and is disrupted in several neurological diseases. Using Organ-Chip technology, we created an entirely human BBB-Chip with induced pluripotent stem cell (iPSC)-derived brain microvascular endothelial-like cells (iBMECs), astrocytes, and neurons. The iBMECs formed a tight monolayer that expressed markers specific to brain vasculature. The BBB-Chip exhibited physiologically relevant transendothelial electrical resistance and accurately predicted blood-to-brain permeability of pharmacologics. Upon perfusing the vascular lumen with whole blood, the microengineered capillary wall protected neural cells from plasma-induced toxicity. Patient-derived iPSCs from individuals with neurological diseases predicted disease-specific lack of transporters and disruption of barrier integrity. By combining Organ-Chip technology and human iPSC-derived tissue, we have created a neurovascular unit that recapitulates complex BBB functions, provides a platform for modeling inheritable neurological disorders, and advances drug screening, as well as personalized medicine.
Vatine, G.D., Barrile, R., Workman, M.J., Sances, S., Barriga, B.K., Rahnama, M., Barthakur, S., Kasendra, M., Lucchesi, C., Kerns, J., Wen, N., Spivia, W.R., Chen, Z., Van Eyk, J., and Svendsen, C.N. Human iPSC-Derived Blood-Brain Barrier Chips Enable Disease Modeling and Personalized Medicine Applications. 04758. 2019 Cell Stem Cell (24):6.
- Engineering Precision Medicine.
- Generation and comprehensive characterization of induced pluripotent stem cells for translational research.