Airway organoids were established from nasal inferior turbinate brush samples of four patients suffering from primary ciliary dyskinesia (PCD), a pulmonary disease caused by dysfunction of the motile cilia in the airways. Airway cells were isolated from the samples and cultivated either in an air-liquid interface or organoid culture. It was shown that organoids can be cultured over extended periods of time when compared to air-liquid interface culture. On the organoids, patient-specific differences in ciliary beating are observed and are in agreement with the patients’ genetic mutations. In comparison to current diagnostic practice, the approach requires a very small amount of donor material and can therefore be seen as an additional and potentially definitive diagnostic assay for PCD patients. Additionally, using genetic editing tools, it was shown that a patient-specific mutation can be repaired. This study demonstrates that patient-derived organoids may become instrumental to obtain cell-biological, diagnostic and therapeutic insights into primary ciliary dyskinesia and other ciliated cell-related diseases.
Modelling of primary ciliary dyskinesia using patient-derived airway organoids
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