AI Article Synopsis
- The study focuses on creating a personalized model system to assess CFTR function using nasal epithelial cells (NECs) from both healthy individuals and cystic fibrosis (CF) patients.
- This involved growing NECs into three-dimensional spheroids and measuring their swelling in response to stimulation, which served as an indicator of CFTR function.
- The results show that these spheroids mimic lung tissue properties and can be used to evaluate the effectiveness of CFTR modulators on specific mutations, paving the way for personalized treatment strategies for CF patients.
Article Abstract
Background: Expansion of CFTR modulators to patients with rare/undescribed mutations will be facilitated by patient-derived models quantifying CFTR function and restoration. We aimed to generate a personalized model system of CFTR function and modulation using non-surgically obtained nasal epithelial cells (NECs).
Methods: NECs obtained by curettage from healthy volunteers and CF patients were expanded and grown in 3-dimensional culture as spheroids, characterized, and stimulated with cAMP-inducing agents to activate CFTR. Spheroid swelling was quantified as a proxy for CFTR function.
Results: NEC spheroids recapitulated characteristics of pseudostratified respiratory epithelia. When stimulated with forskolin/IBMX, spheroids swelled in the presence of functional CFTR, and shrank in its absence. Spheroid swelling quantified mutant CFTR restoration in F508del homozygous cells using clinically available CFTR modulators.
Conclusions: NEC spheroids hold promise for understanding rare CFTR mutations and personalized modulator testing to drive evaluation for CF patients with common, rare or undescribed mutations. Portions of this data have previously been presented in abstract form at the 2016 meetings of the American Thoracic Society and the 2016 North American Cystic Fibrosis Conference.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5868354 | PMC |
| http://dx.doi.org/10.1016/j.jcf.2017.06.010 | DOI Listing |
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