Towards an in vitro model of lung fibrosis
Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive lung disease with no curative treatment to date. The exact pathogenesis underlying IPF remains elusive, but repeated microinjuries to the alveolar epithelium are considered as starting point in the development of IPF.
To investigate the cellular and molecular interactions in the healing alveolar epithelium, we developed wounding assays in phenotypic in vitro models.
Using hydrodynamic flow focusing in microfluidic platforms, we achieved injuries as small as 40 μm. Further, tailored injury positioning, multiple and acid-induced wounding were demonstrated. Upon wounding, Hepatocyte Growth Factor (HGF), an anti-fibrotic agent, markedly accelerated alveolar regeneration. Physiologic stretch, on the other hand, was shown to delay alveolar wound closure in vitro.
The proposed wound healing assays allow, for the first time, to inflict microinjuries with dimensions relevant to the size of a human alveolus. Further, key aspects of the cellular microenvironment, such as moderate acid exposure, multi-focal wounding or physiologic stretching, could be modelled in vitro.
Advanced in vitro models mimic the cellular microenvironment and its alterations in IPF in a physiologically more realistic manner than conventional systems. Such models may thus substantially contribute to the better understanding and, in the near future, more efficient pre-clinical drug testing in IPF.