Journal article
Porcine airway tissue explant culture at a hydrogel-air interface to model submucosal glands in cystic fibrosis progression and therapy
Science advances, Vol.11(47), eady4866
11/21/2025
DOI: 10.1126/sciadv.ady4866
PMCID: PMC12629201
PMID: 41259503
Abstract
Submucosal glands (SMGs) are critical for airway health; however, replicating their complex structure and function outside the body remains challenging. Here, we establish a method of airway tissue explant culture at a hydrogel-air interface (i.e., AirTECH) using trachea from newborn pigs. After 14 days, AirTECH tissues maintain their natural SMG structures, cell types, gene expression, and defense functions, along with intact surface epithelia, smooth muscle, and cartilage. Using AirTECH tissue as a model, we evaluated SMGs in cystic fibrosis (CF) airway disease progression, where exposure to lipopolysaccharide of
caused abnormal mucus obstruction and overexpression of MUC5AC in SMGs, a characteristic feature of CF airway disease. We also explored the contribution of SMGs in airway gene therapy, where green fluorescent protein-encoding adenovirus vectors were transduced and expressed exclusively in airway surface epithelia but not SMGs. These data support AirTECH as a model to understand SMGs in airway disease and test therapeutic interventions.
Details
- Title: Subtitle
- Porcine airway tissue explant culture at a hydrogel-air interface to model submucosal glands in cystic fibrosis progression and therapy
- Creators
- Kaleb C Bierstedt - University of IowaMeng-Hsuan Lin - University of Iowa, Roy J. Carver Department of Biomedical EngineeringWenjie Yu - University of IowaAshley L Cooney - University of IowaBrian J Goodell - University of IowaHuiyu Gong - University of IowaAlejandro A Pezzulo - University of IowaPatrick L Sinn - University of IowaYuliang Xie - University of Iowa, Roy J. Carver Department of Biomedical Engineering
- Resource Type
- Journal article
- Publication Details
- Science advances, Vol.11(47), eady4866
- DOI
- 10.1126/sciadv.ady4866
- PMID
- 41259503
- PMCID
- PMC12629201
- NLM abbreviation
- Sci Adv
- ISSN
- 2375-2548
- eISSN
- 2375-2548
- Publisher
- AMER ASSOC ADVANCEMENT SCIENCE
- Grant note
- Carver Faculty Start-Up FundsNational Institutes of Health: R21 HL161499, R01 EB03339, R01 HL133089, R01 HL171035 Cystic Fibrosis Foundation: 003140I221 Parker B. Francis Fellowship
This work was supported by Carver Faculty Start-Up Funds to Y.X., National Institutes of Health grant R21 HL161499 to Y.X., National Institutes of Health grant R01 EB03339 to Y.X., Cystic Fibrosis Foundation grant 003140I221 to Y.X., National Institutes of Health grant R01 HL133089 to P.L.S., and National Institutes of Health grant R01 HL171035 to P.L.S. W.Y. was supported by a Parker B. Francis Fellowship.
- Language
- English
- Date published
- 11/21/2025
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Pulmonary, Critical Care, and Occupational Medicine; Microbiology and Immunology; Pulmonary Medicine; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Internal Medicine
- Record Identifier
- 9985033876902771
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