RT Journal Article
SR Electronic
T1 Nasal epithelial cell culture fluorescence recovery after photobleaching predicts cystic fibrosis therapeutic response
JF ERJ Open Research
JO erjor
FD European Respiratory Society
SP 00382-2022
DO 10.1183/23120541.00382-2022
VO 8
IS 4
A1 Timothy E. Corcoran
A1 Carol A. Bertrand
A1 Michael M. Myerburg
A1 Daniel J. Weiner
A1 Sheila A. Frizzell
A1 Anna Li
A1 Brittani Agostini
A1 Robert S. Parker
A1 Monica E. Shapiro
A1 Ashok Muthukrishnan
A1 Nicholas D. Hages
A1 Brian P. Mulhern
A1 Joseph M. Pilewski
YR 2022
UL http://openres.ersjournals.com/content/8/4/00382-2022.abstract
AB Background Human nasal epithelial (HNE) cells can be sampled noninvasively and cultured to provide a model of the airway epithelium that reflects cystic fibrosis (CF) pathophysiology. We hypothesised that in vitro measures of HNE cell physiology would correlate directly with in vivo measures of lung physiology and therapeutic response, providing a framework for using HNE cells for therapeutic development and precision medicine.Methods We sampled nasal cells from participants with CF (CF group, n=26), healthy controls (HC group, n=14) and single CF transmembrane conductance regulator (CFTR) mutation carrier parents of the CF group (CR group, n=16). Participants underwent lung physiology and sweat chloride testing, and nuclear imaging-based measurement of mucociliary clearance (MCC) and small-molecule absorption (ABS). CF participants completed a second imaging day that included hypertonic saline (HS) inhalation to assess therapeutic response in terms of MCC. HNE measurements included Ussing chamber electrophysiology, small-molecule and liquid absorption rates, and particle diffusion rates through the HNE airway surface liquid (ASL) measured using fluorescence recovery after photobleaching (FRAP).Results Long FRAP diffusion times were associated with increased MCC response to HS in CF. This implies a strong relationship between inherent factors affecting ASL mucin concentration and therapeutic response to a hydrating therapy. MCC decreased with age in the CR group, which had a larger range of ages than the other two groups. Likely this indicates a general age-related effect that may be accentuated in this group. Measures of lung ABS correlated with sweat chloride in both the HC and CF groups, indicating that CFTR function drives this measure of paracellular small-molecule probe absorption.Conclusions Our results demonstrate the utility of HNE cultures for assessing therapeutic response for hydrating therapies. In vitro measurements of FRAP were particularly useful for predicting response and for characterising important properties of ASL mucus that were ultimately reflected in lung physiology.Measurements in nasal cell cultures can be used to predict therapeutic response in the lungs of cystic fibrosis patients and pulmonary function in healthy controls https://bit.ly/3ClgpbB