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

Authors
 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  ;  YongTae Kim 
Citation
 NATURE COMMUNICATIONS, Vol.11(1) : 175, 2020 
Journal Title
 NATURE COMMUNICATIONS 
Issue Date
2020
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.
Files in This Item:
T202000161.pdf Download
DOI
10.1038/s41467-019-13896-7
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Medical Engineering (의학공학교실) > 1. Journal Papers
Yonsei Authors
Sung, Hak-Joon(성학준) ORCID logo https://orcid.org/0000-0003-2312-2484
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/174923
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