collection-expansion-differentiation-primary-human-nasal-epithelial

Collection, Expansion, and Differentiation of Primary Human Nasal Epithelial Cell Models for Quantification of Cilia Beat Frequency

Measurements of cilia function (beat frequency, pattern) have been established as diagnostic tools for respiratory diseases such as primary ciliary ...

University of New South Wales

Sydney Children's Hospital

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.

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

Cholecystoduodenostomy is a surgical procedure that bypasses the extrahepatic biliary tree and connects the gallbladder directly to the duodenum. This case describes the successful use of this procedure in a novel situation.

Case report: Cholecystoduodenostomy for cholestatic liver disease in a premature infant with cystic fibrosis and short gut syndrome.

Patient-derived airway cells differentiated at Air Liquid Interface (ALI) are valuable models for Cystic fibrosis (CF) precision therapy. Different culture expansion methods have been established to extend expansion capacity of airway basal cells, while retaining functional airway epithelium physiology. Considerable variation in response to CFTR modulators is observed in cultures even within the same CFTR genotype and despite the use of similar ALI culture techniques. We aimed to address culture expansion method impact on differentiation.

Significant functional differences in differentiated Conditionally Reprogrammed (CRC)- and Feeder-free Dual SMAD inhibited-expanded human nasal epithelial cells.

Patient-oriented research approaches that reflect the needs and priorities of those most affected by health research outcomes improves translation of research findings into practice. Targeted therapies for cystic fibrosis (CF) are now a viable treatment option for some eligible individuals despite the heterogeneous patient-specific therapeutic response. This has necessitated development of a clinical tool that predicts treatment response for individual patients. Patient-derived mini-organs (organoids) have been at the forefront of this development. However, little is known about their acceptability in CF patients and members of the public.

Article	Year
Human Primary Epithelial Cell Models: Promising Tools in the Era of Cystic Fibrosis Personalized Medicine. Frontiers in pharmacology\| PubMed ID: 30581387
Case report: Cholecystoduodenostomy for cholestatic liver disease in a premature infant with cystic fibrosis and short gut syndrome. BMC pediatrics\| PubMed ID: 30857526	2019
Significant functional differences in differentiated Conditionally Reprogrammed (CRC)- and Feeder-free Dual SMAD inhibited-expanded human nasal epithelial cells. Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society\| PubMed ID: 33414087
Avatar acceptability: views from the Australian Cystic Fibrosis community on the use of personalised organoid technology to guide treatment decisions. ERJ open research\| PubMed ID: 33532470

Laura K. Fawcett

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