The DOI matches its Crossref record; 47 of the 47 references it cites were found in a registry or an index.
Blood-brain-barrier spheroids as an in vitro screening platform for brain-penetrating agents
Open accessAbstract
Culture-based blood–brain barrier (BBB) models are crucial tools to enable rapid screening of brain-penetrating drugs. However, reproducibility of in vitro barrier properties and permeability remain as major challenges. Here, we report that self-assembling multicellular BBB spheroids display reproducible BBB features and functions. The spheroid core is comprised mainly of astrocytes, while brain endothelial cells and pericytes encase the surface, acting as a barrier that regulates transport of molecules. The spheroid surface exhibits high expression of tight junction proteins, VEGF-dependent permeability, efflux pump activity and receptor-mediated transcytosis of angiopep-2. In contrast, the transwell co-culture system displays comparatively low levels of BBB regulatory proteins, and is unable to discriminate between the transport of angiopep-2 and a control peptide. Finally, we have utilized the BBB spheroids to screen and identify BBB-penetrant cell-penetrating peptides (CPPs). This robust in vitro BBB model could serve as a valuable next-generation platform for expediting the development of CNS therapeutics.
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Citations
Cites
Astrocyte-endothelial interactions at the blood-brain barrier
Abbott, N. J., Rönnbäck, L., & Hansson, E. (2006) · Nature Reviews Neuroscience · doi:10.1038/nrn1824 · Cited by 5,595
The Blood-Brain Barrier in Health and Chronic Neurodegenerative Disorders
Zlokovic, B. V. (2008) · Neuron · doi:10.1016/j.neuron.2008.01.003 · Cited by 3,280
Tight junctions of the blood–brain barrier
Wolburg, H., & Lippoldt, A. (2002) · Vascular Pharmacology · doi:10.1016/s1537-1891(02)00200-8 · Cited by 1,183
Mechanisms of Cellular Uptake of Cell-Penetrating Peptides
Madani, F., Lindberg, S., Langel, Ü., Futaki, S., & Gräslund, A. (2011) · Journal of Biophysics · doi:10.1155/2011/414729 · Cited by 984
P-Glycoprotein, a gatekeeper in the blood–brain barrier
Schinkel, A. H. (1999) · Advanced Drug Delivery Reviews · doi:10.1016/s0169-409x(98)00085-4 · Cited by 960
Pathophysiological consequences of VEGF-induced vascular permeability
Weis, S. M., & Cheresh, D. A. (2005) · Nature · doi:10.1038/nature03987 · Cited by 909
Quantitative targeted absolute proteomics of human blood-brain barrier transporters and receptors
Uchida, Y., Ohtsuki, S., Katsukura, Y., Ikeda, C., Suzuki, T., Kamiie, J., & Terasaki, T. (2011) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2011.07208.x · Cited by 881
The hCMEC/D3 cell line as a model of the human blood brain barrier
Weksler, B., Romero, I. A., & Couraud, P.-O. (2013) · Fluids and Barriers of the CNS · doi:10.1186/2045-8118-10-16 · Cited by 753
Characterization of a microfluidic in vitro model of the blood-brain barrier (μBBB)
Booth, R., & Kim, H. (2012) · Lab on a Chip · doi:10.1039/c2lc40094d · Cited by 739
Endothelial Cell Heterogeneity
Aird, W. C. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a006429 · Cited by 731
Cited by
Campisi, M., Shin, Y., Osaki, T., Hajal, C., Chiono, V., & Kamm, R. D. (2018) · Biomaterials · doi:10.1016/j.biomaterials.2018.07.014 · Cited by 718
Xie, J., Bi, Y., Zhang, H., Dong, S., Teng, L., Lee, R. J., & Yang, Z. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.00697 · Cited by 466
Wevers, N. R., Kasi, D. G., Gray, T., Wilschut, K. J., Smith, B., van Vught, R., Shimizu, F., Sano, Y., Kanda, T., Marsh, G., et al. (2018) · Fluids and Barriers of the CNS · doi:10.1186/s12987-018-0108-3 · Cited by 353
Blood–brain-barrier organoids for investigating the permeability of CNS therapeutics
Bergmann, S., Lawler, S. E., Qu, Y., Fadzen, C. M., Wolfe, J. M., Regan, M. S., Pentelute, B. L., Agar, N. Y. R., & Cho, C.-F. (2018) · Nature Protocols · doi:10.1038/s41596-018-0066-x · Cited by 285
Self-citationA Novel Transwell Blood Brain Barrier Model Using Primary Human Cells
Stone, N. L., England, T. J., & O’Sullivan, S. E. (2019) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2019.00230 · Cited by 251
Metadata
- Authors
- Cho, C.-F., Wolfe, J. M., Fadzen, C. M., Calligaris, D., Hornburg, K., Chiocca, E. A., Agar, N. Y. R., Pentelute, B. L., & Lawler, S. E.
- Venue
- Nature Communications
- Published
- 2017-06-06
- Volume
- 8
- Issue
- 1
- Pages
- 15623-15623
- ISSN
- 2041-1723 (ISSN-L)
- OpenAlex
- W2624368609
- Cited by
- 336
- References
- 47
- FWCI
- 9.40
- Type
- journal article
- Language
- en
- Open access
- gold
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- Cho, C.-F., Wolfe, J. M., Fadzen, C. M., Calligaris, D., Hornburg, K., Chiocca, E. A., Agar, N. Y. R., Pentelute, B. L., & Lawler, S. E. (2017). Blood-brain-barrier spheroids as an in vitro screening platform for brain-penetrating agents. Nature Communications. https://doi.org/10.1038/ncomms15623
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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