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Frontiers in pharmacology
2018;9 1429.

Human Primary Epithelial Cell Models: Promising Tools in the Era of Cystic Fibrosis Personalized Medicine.

Nikhil T Awatade, Sharon L Wong, Chris K Hewson, Laura K Fawcett, Anthony Kicic, Adam Jaffe, Shafagh A Waters
Author Information
  1. Nikhil T Awatade: Faculty of Medicine, School of Women's and Children's Health, University of New South Wales, Sydney, NSW, Australia.
  2. Sharon L Wong: Faculty of Medicine, School of Women's and Children's Health, University of New South Wales, Sydney, NSW, Australia.
  3. Chris K Hewson: Faculty of Medicine, School of Women's and Children's Health, University of New South Wales, Sydney, NSW, Australia.
  4. Laura K Fawcett: Faculty of Medicine, School of Women's and Children's Health, University of New South Wales, Sydney, NSW, Australia.
  5. Anthony Kicic: Centre for Child Health Research, Telethon Kids Institute, The University of Western Australia, Nedlands, WA, Australia.
  6. Adam Jaffe: Faculty of Medicine, School of Women's and Children's Health, University of New South Wales, Sydney, NSW, Australia.
  7. Shafagh A Waters: Faculty of Medicine, School of Women's and Children's Health, University of New South Wales, Sydney, NSW, Australia.
PMID: 30581387 DOI: 10.3389/fphar.2018.01429

Abstract

Cystic fibrosis (CF) is an inherited disorder where individual disease etiology and response to therapeutic intervention is impacted by CF transmembrane regulator (CFTR) mutations and other genetic modifiers. CFTR regulates multiple mechanisms in a diverse range of epithelial tissues. In this Review, we consolidate the latest updates in the development of primary epithelial cellular model systems relevant for CF. We discuss conventional two-dimensional (2-D) airway epithelial cell cultures, the backbone of cellular models to date, as well as improved expansion protocols to overcome finite supply of the cellular source. We highlight a range of strategies for establishment of three dimensional (3-D) airway and intestinal organoid models and evaluate the limitations and potential improvements in each system, focusing on their application in CF. The CFTR functional assays in patient-derived organoids allow for preclinical pharmacotherapy screening to identify responsive patients. It is likely that organoids will be an invaluable preclinical tool to unravel disease mechanisms, design novel treatments, and enable clinicians to provide personalized management for patients with CF.

Keywords

CFTR CFTR modulator cystic fibrosis drug development organoid personalized medicine sweat chloride

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