RT Journal Article
SR Electronic
T1 Nasal epithelial cell culture FRAP predicts cystic fibrosis therapeutic response
JF ERJ Open Research
JO erjor
FD European Respiratory Society
SP 00382-2022
DO 10.1183/23120541.00382-2022
A1 Corcoran, Timothy E
A1 Bertrand, Carol A
A1 Myerburg, Michael M.
A1 Weiner, Daniel J.
A1 Frizzell, Sheila A.
A1 Li, Anna
A1 Agostini, Brittani
A1 Parker, Robert S.
A1 Shapiro, R. Monica E.
A1 Muthukrishnan, Ashok
A1 Hages, Nicholas D.
A1 Mulhern, Brian P.
A1 Pilewski, Joseph M.
YR 2022
UL http://openres.ersjournals.com/content/early/2022/09/22/23120541.00382-2022.abstract
AB Human nasal epithelial (HNE) cells can be sampled non-invasively and cultured to provide a model of the airway epithelium that reflects cystic fibrosis (CF) pathophysiology. We hypothesized 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 HNEs for therapeutic development and precision medicine. We sampled nasal cells from participants with CF (CF, n=26), healthy controls (HC, n=14), and the single mutation carrier parents of the CF group (CR, 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 measured using fluorescence recovery after photobleaching (FRAP). 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.FootnotesThis manuscript has recently been accepted for publication in the ERJ Open Research. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJOR online. Please open or download the PDF to view this article.Conflict of Interest: The authors have nothing to disclose.