4.7 Article

A High-Throughput Distal Lung Air-Blood Barrier Model Enabled By Density-Driven Underside Epithelium Seeding

期刊

ADVANCED HEALTHCARE MATERIALS
卷 10, 期 15, 页码 -

出版社

WILEY
DOI: 10.1002/adhm.202100879

关键词

bioassays; coculture; high-throughput; inflammation; lungs; screening

资金

  1. BioMAT Training Grant under National Institutes of Health (NIH) [5T32EB006343-10]
  2. National Center for Advancing Translational Sciences of the NIH [UL1TR002378]
  3. Petit Undergraduate Research Fellowship
  4. Mentored Patient-Oriented Research Career Development Award from the NIH [1K23HL151897-01]
  5. National Science Foundation Early-Concept Grants for Exploratory Research (EAGER) Award [2032273]
  6. NIH [5R01HL136141-04]
  7. Wallace H. Coulter Department of Biomedical Engineering's COVID-19 Seed Grant Award
  8. Emory University Research Committee Award
  9. Div Of Chem, Bioeng, Env, & Transp Sys
  10. Directorate For Engineering [2032273] Funding Source: National Science Foundation

向作者/读者索取更多资源

The paper describes a new seeding method for a high-throughput tissue model of the distal lung epithelium-endothelium barrier, eliminating the need for inversion traditionally required in such models. The model exhibits mature barrier function and appropriate response to inflammatory stimuli, making it suitable for studying disease therapies and pathogen infections.
High-throughput tissue barrier models can yield critical insights on how barrier function responds to therapeutics, pathogens, and toxins. However, such models often emphasize multiplexing capability at the expense of physiologic relevance. Particularly, the distal lung's air-blood barrier is typically modeled with epithelial cell monoculture, neglecting the substantial contribution of endothelial cell feedback in the coordination of barrier function. An obstacle to establishing high-throughput coculture models relevant to the epithelium/endothelium interface is the requirement for underside cell seeding, which is difficult to miniaturize and automate. Therefore, this paper describes a scalable, low-cost seeding method that eliminates inversion by optimizing medium density to float cells so they attach under the membrane. This method generates a 96-well model of the distal lung epithelium-endothelium barrier with serum-free, glucocorticoid-free air-liquid differentiation. The polarized epithelial-endothelial coculture exhibits mature barrier function, appropriate intercellular junction staining, and epithelial-to-endothelial transmission of inflammatory stimuli such as polyinosine:polycytidylic acid (poly(I:C)). Further, exposure to influenza A virus PR8 and human beta-coronavirus OC43 initiates a dose-dependent inflammatory response that propagates from the epithelium to endothelium. While this model focuses on the air-blood barrier, the underside seeding method is generalizable to various coculture tissue models for scalable, physiologic screening.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.7
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据