Utilising human cellular models of primary ciliary dyskinesia: a scoping review.

Abstract

Background: Primary ciliary dyskinesia (PCD) comprises a group of rare genetic disorders that primarily affect the function of motile respiratory cilia, leading to progressive sinopulmonary disease. Disease models can be used to investigate potential therapies or responses to environmental exposures. We sought to identify and describe knowledge gaps in the modelling approaches and outcome measures used in applied in vitro or ex vivo human respiratory cellular models of PCD.

Methods: We conducted a scoping review of Medline and Embase (2000-2024), screening studies of in vitro or ex vivo human respiratory cellular models of PCD and charted modelling approaches, applications and outcome measures.

Results: Of the 612 screened abstracts, 10 articles were included in the qualitative synthesis. The modelling approaches included primary cell culture at an air-liquid interface (ALI) (n=5), spheroid culture (n=2), organoid culture (n=2) and induced pluripotent stem cell-derived ALI culture (n=1). Modelling protocols were heterogenous. Applications included 1) therapeutic gene correction or replacement applications (n=4) and therapeutic drug screening (n=1), or 2) exposure to infection (n=4), drugs (n=3) and house dust mite allergen (n=1). Outcome measures used for both model characterisation and evaluation of therapeutic interventions were inconsistent. Certain outcome measures, such as ciliary function, were reported inconsistently, which limited interpretability of findings.

Conclusion: A variety of PCD models exist but a lack of standardised characterisation hinders the reproducibility and comparability of findings. Consensus is needed on the minimum requirements for model characterisation and standardised reporting of outcome measures, which will facilitate model development for therapeutic and exposure applications.