@article{b9053ec6b63a412da8925bb118aba269,
title = "Modelling of primary ciliary dyskinesia using patient-derived airway organoids",
abstract = "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.",
keywords = "airway organoids, ciliated cell, primary ciliary dyskinesia, pulmonary differentiation, DIAGNOSIS, CELLS, METAPLASIA, CULTURES",
author = "{Van der Vaart}, J. and L. Bottinger and M.H. Geurts and {Van de Wetering}, W.J. and K. Knoops and N. Sachs and H. Begthel and J. Korving and C. Lopez-Iglesias and P.J. Peters and K. Eitan and A. Gileles-Hillel and H. Clevers",
note = "Funding Information: We thank A. de Graaff and the Hubrecht Imaging Centre (HIC) for microscopy assistance and the Utrecht Sequencing Facility (subsidized by the University Medical Centre Utrecht, Hubrecht Institute, Utrecht University and NWO project 184.034.019). We thank Medical Microbiology of the University Medical Centre Utrecht for the help with scanning electron microscopy. We thank Talya Dayton and Amanda Andersson-Rolf for their help with writing the manuscript, Carola Ammerlaan for her help with flow cytometry experiments and analysis. This work was supported by the gravitation programme CancerGenomiCs.nl from the Netherlands Organisation for Scientific Research. Funding Information: We thank A. de Graaff and the Hubrecht Imaging Centre (HIC) for microscopy assistance and the Utrecht Sequencing Facility (subsidized by the University Medical Centre Utrecht, Hubrecht Institute, Utrecht University and NWO project 184.034.019). We thank Medical Microbiology of the University Medical Centre Utrecht for the help with scanning electron microscopy. We thank Talya Dayton and Amanda Andersson‐Rolf for their help with writing the manuscript, Carola Ammerlaan for her help with flow cytometry experiments and analysis. This work was supported by the gravitation programme CancerGenomiCs.nl from the Netherlands Organisation for Scientific Research. Publisher Copyright: {\textcopyright} 2021 The Authors. Published under the terms of the CC BY 4.0 license",
year = "2021",
month = dec,
day = "6",
doi = "10.15252/embr.202052058",
language = "English",
volume = "22",
journal = "Embo Reports",
issn = "1469-221X",
publisher = "Wiley",
number = "12",
}