Human iPSC-Derived Blood-Brain Barrier Chips Enable Disease Modeling and Personalized Medicine Applications

Cell Stem Cell. 2019 Jun 6;24(6):995-1005.e6. doi: 10.1016/j.stem.2019.05.011.


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.

Keywords: BBB; MCT8; blood-brain barrier; disease model; iPSCs; neural; neurological disease; organ-on-chip; personalized medicine; thyroid.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Astrocytes / physiology*
  • Bioengineering
  • Blood-Brain Barrier / pathology
  • Blood-Brain Barrier / physiology*
  • Brain / physiology*
  • Capillary Permeability
  • Cell Differentiation
  • Cells, Cultured
  • Drug Evaluation, Preclinical
  • Endothelium, Vascular / physiology*
  • Humans
  • Induced Pluripotent Stem Cells / physiology*
  • Microfluidics / methods*
  • Neurons / physiology*
  • Organ Culture Techniques
  • Precision Medicine