Authors: Alice Bough (Future Science Group)
Researchers from Cedars-Sinai Medical Center (CA, USA) have created a blood–brain barrier (BBB) chip utilizing human induced pluripotent stem cells (iPSCs). Their paper, published in Cell Stem Cell, presents a novel method for analyzing drug interactions with the BBB and could also be utilized to further our understanding of neurological disorders.
Conditions such as Parkinson’s disease, Huntington’s disease and amyotrophic lateral sclerosis have been linked to defects in the BBB. To learn more about the role of the BBB in these diseases the research group combined Organ–Chip technology with human iPSC-derived tissue to create a BBB chip.
They utilized pluripotent stem cells to develop brain microvascular endothelial-like cells, neurons and astrocytes. These were then used to form a cellular layer that expressed markers characteristic to brain vasculature.
The authors confirmed that the BBB chip recreated natural physiological conditions such as the relevant transendothelial electrical resistance and the ability to selectively filter certain molecules and drugs.
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The BBB chip was created using both iPSCs from healthy individuals and those from patients with neurological conditions. In the cases in which the BBB was derived from patients with neurological disorders, the barriers displayed structural disruption and also lacked certain receptors, mimicking the disease phenotypes.
In addition to providing a new platform on which to test drug permeability through the BBB, the authors of the paper hope that this BBB chip technology can be utilized on an individual basis to identify which drugs will be most effective to treat different neurological conditions.
“The study’s findings open a promising pathway for precision medicine,” commented Clive Svendsen (Cedars-Sinai Medical Center). “The possibility of using a patient-specific, multicellular model of a BBB on a chip represents a new standard for developing predictive, personalized medicine”.
Sources: Vatine GD, Barrile R, Workman MJ et al. Human iPSC-derived blood-brain barrier chips enable disease modeling and personalized medicine applications. Cell Stem Cell 24(6), 995–1005 (2019); www.cedars-sinai.org/newsroom/scientists-recreate-blood-brain-barrier-defect-outside-the-body