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

Gad D. Vatine, Riccardo Barrile, Michael J. Workman, Samuel Sances, Bianca K. Barriga, Matthew Rahnama, Sonalee Barthakur, Magdalena Kasendra, Carolina Lucchesi, Jordan Kerns, Norman Wen, Weston R. Spivia, Zhaohui Chen, Jennifer Van Eyk, Clive N. Svendsen

Research output: Contribution to journalArticlepeer-review

141 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)995-1005.e6
JournalCell Stem Cell
Volume24
Issue number6
DOIs
StatePublished - 6 Jun 2019

Keywords

  • BBB
  • MCT8
  • blood-brain barrier
  • disease model
  • iPSCs
  • neural
  • neurological disease
  • organ-on-chip
  • personalized medicine
  • thyroid

Fingerprint

Dive into the research topics of 'Human iPSC-Derived Blood-Brain Barrier Chips Enable Disease Modeling and Personalized Medicine Applications'. Together they form a unique fingerprint.

Cite this