An Ovine Model Yields Histology and Gene Expression Changes Consistent with Laryngotracheal Stenosis.
idiopathic subglottic stenosis
large animal model
laryngotracheal stenosis
ovine model
Journal
The Laryngoscope
ISSN: 1531-4995
Titre abrégé: Laryngoscope
Pays: United States
ID NLM: 8607378
Informations de publication
Date de publication:
13 May 2024
13 May 2024
Historique:
revised:
06
04
2024
received:
08
02
2024
accepted:
24
04
2024
medline:
13
5
2024
pubmed:
13
5
2024
entrez:
13
5
2024
Statut:
aheadofprint
Résumé
Animal models for laryngotracheal stenosis (LTS) are critical to understand underlying mechanisms and study new therapies. Current animal models for LTS are limited by small airway sizes compared to human. The objective of this study was to develop and validate a novel, large animal ovine model for LTS. Sheep underwent either bleomycin-coated polypropylene brush injury to the subglottis (n = 6) or airway stent placement (n = 2) via suspension microlaryngoscopy. Laryngotracheal complexes were harvested 4 weeks following injury or stent placement. For the airway injury group, biopsies (n = 3 at each site) were collected of tracheal scar and distal normal regions, and analyzed for fibrotic gene expression. Lamina propria (LP) thickness was compared between injured and normal areas of trachea. No mortality occurred in sheep undergoing airway injury or stent placement. There was no migration of tracheal stents. After protocol optimization, LP thickness was significantly increased in injured trachea (Sheep #3: 529.0 vs. 850.8 um; Sheep #4: 933.0 vs. 1693.2 um; Sheep #5: 743.7 vs. 1378.4 um; Sheep #6: 305.7 vs. 2257.6 um). A significant 62-fold, 20-fold, 16-fold, 16-fold, and 9-fold change of COL1, COL3, COL5, FN1, and TGFB1 was observed in injured scar specimen relative to unaffected airway, respectively. An ovine LTS model produces histologic and transcriptional changes consistent with fibrosis seen in human LTS. Airway stent placement in this model is safe and feasible. This large airway model is a reliable and reproducible method to assess the efficacy of novel LTS therapies prior to clinical translation. N/A Laryngoscope, 2024.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : National Institute of Health
ID : R01DC018567
Organisme : National Institute of Health
ID : R56DC020736
Informations de copyright
© 2024 The American Laryngological, Rhinological and Otological Society, Inc.
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