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Modelling of primary ciliary dyskinesia using patient‐derived airway organoids
Author(s) -
van der Vaart Jelte,
Böttinger Lena,
Geurts Maarten H,
van de Wetering Willine J,
Knoops Kèvin,
Sachs Norman,
Begthel Harry,
Korving Jeroen,
LopezIglesias Carmen,
Peters Peter J,
Eitan Kerem,
GilelesHillel Alex,
Clevers Hans
Publication year - 2021
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.202052058
Subject(s) - primary ciliary dyskinesia , organoid , cilium , airway , motile cilium , phenotype , mutation , biology , medicine , microbiology and biotechnology , pathology , lung , genetics , gene , bronchiectasis , surgery
Patient‐derived human organoids can be used to model a variety of diseases. Recently, we described conditions for long‐term expansion of human airway organoids (AOs) directly from healthy individuals and patients. Here, we first optimize differentiation of AOs towards ciliated cells. After differentiation of the AOs towards ciliated cells, these can be studied for weeks. When returned to expansion conditions, the organoids readily resume their growth. We apply this condition to AOs established from nasal inferior turbinate brush samples of patients suffering from primary ciliary dyskinesia (PCD), a pulmonary disease caused by dysfunction of the motile cilia in the airways. Patient‐specific differences in ciliary beating are observed and are in agreement with the patients' genetic mutations. More detailed organoid ciliary phenotypes can thus be documented in addition to the standard diagnostic procedure. Additionally, using genetic editing tools, we show that a patient‐specific mutation can be repaired. This study demonstrates the utility of organoid technology for investigating hereditary airway diseases such as PCD.