An in situ, in vivo murine model for the study of laryngotracheal stenosis

Research output: Contribution to journalArticle

Abstract

IMPORTANCE: Laryngotracheal stenosis (LTS) lacks an ideal animal model to study its unique wound-healing pathophysiology and the effect of interventions. OBJECTIVE: To present an in vivo, in situ mouse model of LTS that can be used to investigate its pathophysiology, mechanisms, and interventions for treatment. DESIGN, SETTING, AND SUBJECTS: Prospective controlled animal study performed at an academic animal research facility on 87 C57BL/6 mice. INTERVENTIONS: Experimental mice (n = 40) underwent bleomycin-coated wire-brush injury to the larynx and trachea, while mechanical injury controls (n = 32) underwent phosphate-buffered saline-coated wire-brush injury. Normal controls (n = 9) underwent no intervention, and mock surgery controls (n = 6) underwent anterior transcervical tracheal exposure only. Laryngotracheal complexes were harvested at days 7, 14, and 21 after injury. At the respective time points, mice in the chemomechanical and mechanical injury groups were killed, and their laryngotracheal complexes were harvested for histologic analysis. Normal and mock surgery controls were killed and then underwent histologic analysis. MAIN OUTCOMES AND MEASURES: The primary outcome measurewas lamina propria thickness. RESULTS: The chemomechanical injury group maintained a significant increase in lamina propria thickness through day 21 compared with uninjured controls at day 7 (82.7 vs 41.8 innodatamum; P<.05), day 14 (93.5 vs 26.0 innodatamum; P<.05), and day 21 (91.2 vs 40.8 innodatamum; P<.05). Compared with the mechanical injury group, the chemomechanical injury group demonstrated a significantly increased thickness at 21 days (91.2 vs 33.7 innodatamum; P<.05). CONCLUSIONS AND RELEVANCE: Chemomechanical initiation of fibrosis in situ creates a viable mouse model of LTS that incorporates the physiologic circulatory supply and airflow. This small-animal model may be used to investigate the pathogenesis and inflammatory mechanisms of iatrogenic LTS and test therapeutic interventions to reverse or reduce the development of fibrosis.

Original languageEnglish (US)
Pages (from-to)961-966
Number of pages6
JournalJAMA Otolaryngology - Head and Neck Surgery
Volume140
Issue number10
DOIs
StatePublished - Oct 1 2014

ASJC Scopus subject areas

  • Surgery
  • Otorhinolaryngology

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