Modelling of primary ciliary dyskinesia using patient-derived airway organoids

TY - JOUR

T1 - Modelling of primary ciliary dyskinesia using patient-derived airway organoids

AU - van der Vaart, Jelte

AU - Böttinger, Lena

AU - Geurts, Maarten H

AU - van de Wetering, Willine J

AU - Knoops, Kèvin

AU - Sachs, Norman

AU - Begthel, Harry

AU - Korving, Jeroen

AU - Lopez-Iglesias, Carmen

AU - Peters, Peter J

AU - Eitan, Kerem

AU - Gileles-Hillel, Alex

AU - Clevers, Hans

N1 - © 2021 The Authors. Published under the terms of the CC BY 4.0 license.

PY - 2021/12/6

Y1 - 2021/12/6

N2 - 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.

AB - 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.

U2 - 10.15252/embr.202052058

DO - 10.15252/embr.202052058

M3 - Article

C2 - 34693619

SN - 1469-221X

VL - 22

SP - e52058

JO - EMBO Reports

JF - EMBO Reports

IS - 12

ER -