Abstract

Limited success achieved in translating basic science discoveries into clinical applications for chronic airway diseases is attributed to differences in respiratory anatomy and physiology, poor approximation of pathologic processes, and lack of correlative clinical endpoints between humans and laboratory animal models. Here, we discuss advantages of using ferrets (Mustela putorus furo) as a model for improved understanding of human airway physiology and demonstrate assays for quantifying airway epithelial ion transport in vivo and ex vivo, and establish air-liquid interface cultures of ferret airway epithelial cells as a complementary in vitro model for mechanistic studies. We present data here that establishes the feasibility of measuring these human disease endpoints in ferrets. Briefly, potential difference across the nasal and the lower airway epithelium in ferrets could be consistently assessed, were highly reproducible, and responsive to experimental interventions. Additionally, ferret airway epithelial cells were amenable to primary cell culture methods for in vitro experiments as was the use of ferret tracheal explants as an ex vivo system for assessing ion transport. The feasibility of conducting multiple assessments of disease outcomes supports the adoption of ferrets as a highly relevant model for research in obstructive airway diseases.

Highlights

  • Obstructive lung diseases such as cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD), and asthma are characterized by a pronounced involvement of the airway epithelium [1]

  • nasal potential difference (NPD) is the voltage across the nasal epithelium, representing the sum of the membrane potentials of the outer epithelial membrane

  • NPD can be used to evaluate ion transport in vivo, including the contributions of CFTR and ENaC, and is a valuable tool for diagnosis and assessment of CF and other airway diseases characterized by chloride and sodium ion transport defects [22]

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Summary

Introduction

Obstructive lung diseases such as cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD), and asthma are characterized by a pronounced involvement of the airway epithelium [1]. These disorders collectively constitute a major cause of morbidity, mortality, and healthcare utilization [2], yet development of novel therapies to lessen disease burden is impeded by lack of animal models and techniques that are informative for elucidating disease biology, identifying new drug targets, and predicting the effect of drug candidates.

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