Microengineered human blood–brain barrier platform for understanding nanoparticle transport mechanisms

Song Ih Ahn, Yoshitaka J. Sei, Hyun-Ji Park, Jinhwan Kim, Yujung Ryu, Jeongmoon J. Choi, Hak-Joon Sung, Tobey J. MacDonald, Allan I. Levey and YongTae Kim ()
Additional contact information
Song Ih Ahn: Georgia Institute of Technology
Yoshitaka J. Sei: Georgia Institute of Technology
Hyun-Ji Park: Georgia Institute of Technology
Jinhwan Kim: Georgia Institute of Technology
Yujung Ryu: Georgia Institute of Technology
Jeongmoon J. Choi: Georgia Institute of Technology
Hak-Joon Sung: Yonsei University College of Medicine
Tobey J. MacDonald: Emory University
Allan I. Levey: Emory University
YongTae Kim: Georgia Institute of Technology

Nature Communications, 2020, vol. 11, issue 1, 1-12

Abstract: Abstract Challenges in drug development of neurological diseases remain mainly ascribed to the blood–brain barrier (BBB). Despite the valuable contribution of animal models to drug discovery, it remains difficult to conduct mechanistic studies on the barrier function and interactions with drugs at molecular and cellular levels. Here we present a microphysiological platform that recapitulates the key structure and function of the human BBB and enables 3D mapping of nanoparticle distributions in the vascular and perivascular regions. We demonstrate on-chip mimicry of the BBB structure and function by cellular interactions, key gene expressions, low permeability, and 3D astrocytic network with reduced reactive gliosis and polarized aquaporin-4 (AQP4) distribution. Moreover, our model precisely captures 3D nanoparticle distributions at cellular levels and demonstrates the distinct cellular uptakes and BBB penetrations through receptor-mediated transcytosis. Our BBB platform may present a complementary in vitro model to animal models for prescreening drug candidates for the treatment of neurological diseases.

Date: 2020
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-019-13896-7 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-019-13896-7

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-019-13896-7

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().