Format

Send to

Choose Destination
Front Pharmacol. 2018 Dec 7;9:1429. doi: 10.3389/fphar.2018.01429. eCollection 2018.

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

Awatade NT1,2, Wong SL1,2, Hewson CK1,2,3, Fawcett LK1,2,4, Kicic A5,6,7,8,9, Jaffe A1,2,4, Waters SA1,2.

Author information

1
Faculty of Medicine, School of Women's and Children's Health, University of New South Wales, Sydney, NSW, Australia.
2
Molecular and Integrative Cystic Fibrosis Research Centre (miCF_RC), School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia.
3
School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, Australia.
4
Department of Respiratory Medicine, Sydney Children's Hospital, Sydney, NSW, Australia.
5
Centre for Child Health Research, Telethon Kids Institute, The University of Western Australia, Nedlands, WA, Australia.
6
Occupation and Environment, School of Public Health, Curtin University, Bentley, WA, Australia.
7
Faculty of Health and Medical Sciences, The University of Western Australia, Nedlands, WA, Australia.
8
Department of Respiratory and Sleep Medicine, Perth Children's Hospital, Nedlands, WA, Australia.
9
Centre for Cell Therapy and Regenerative Medicine, School of Medicine and Pharmacology, The University of Western Australia, Nedlands, WA, Australia.

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 in vitro 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 in vitro 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

Supplemental Content

Full text links

Icon for Frontiers Media SA Icon for PubMed Central
Loading ...
Support Center