The potential of microfluidic lung epithelial wounding: towards in vivo-like alveolar microinjuries

Integr Biol (Camb). 2014 Dec;6(12):1132-40. doi: 10.1039/c4ib00149d. Epub 2014 Sep 10.

Abstract

Idiopathic pulmonary fibrosis (IPF) remains a major clinical challenge to date. Repeated alveolar epithelial microinjuries are considered as the starting point and the key event in both the development and the progression of IPF. Various pro-fibrotic agents have been identified and shown to cause alveolar damage. In IPF, however, no leading cause of alveolar epithelial microinjuries can be identified and the exact etiology remains elusive. New results from epidemiologic studies suggest a causal relation between IPF and frequent episodes of gastric refluxes resulting in gastric microaspirations into the lung. The effect of gastric contents on the alveolar epithelium has not been investigated in detail. Here, we present a microfluidic lung epithelial wounding system that allows for the selective exposure of alveolar epithelial cells to gastric contents. The system is revealed to be robust and highly reproducible. The thereby created epithelial microwounds are of tiny dimensions and best possibly reproduce alveolar damage in the lung. We further demonstrate that exposure to gastric contents, namely hydrochloric acid (HCl) and pepsin, directly damages the alveolar epithelium. Together, this novel in vitro wounding system allows for the creation of in vivo-like alveolar microinjuries with the potential to study lung injury and alveolar wound repair in vitro.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Equipment Design
  • Equipment Failure Analysis
  • Feasibility Studies
  • Flow Injection Analysis / instrumentation
  • Flow Injection Analysis / methods
  • Gastroesophageal Reflux / chemically induced
  • Gastroesophageal Reflux / pathology
  • Humans
  • Hydrochloric Acid*
  • Idiopathic Pulmonary Fibrosis / chemically induced*
  • Idiopathic Pulmonary Fibrosis / pathology*
  • Microfluidic Analytical Techniques / instrumentation*
  • Microfluidic Analytical Techniques / methods
  • Pulmonary Alveoli / drug effects
  • Pulmonary Alveoli / injuries*
  • Pulmonary Alveoli / pathology
  • Respiratory Mucosa / drug effects
  • Respiratory Mucosa / injuries*
  • Respiratory Mucosa / pathology*

Substances

  • Hydrochloric Acid