Engineering rotating apical-out airway organoid for assessing respiratory cilia motility

Autor: Piyumi Wijesekara, Prakarsh Yadav, Lydia A. Perkins, Donna B. Stolz, Jonathan M. Franks, Simon C. Watkins, Emily Reinoso Jacome, Steven L. Brody, Amjad Horani, Jian Xu, Amir Barati Farimani, Xi Ren
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: iScience, Vol 25, Iss 8, Pp 104730- (2022)
Druh dokumentu: article
ISSN: 2589-0042
DOI: 10.1016/j.isci.2022.104730
Popis: Summary: Motile cilia project from the airway apical surface and directly interface with inhaled external environment. Owing to cilia’s nanoscale dimension and high beating frequency, quantitative assessment of their motility remains a sophisticated task. Here we described a robust approach for reproducible engineering of apical-out airway organoid (AOAO) from a defined number of cells. Propelled by exterior-facing cilia beating, the mature AOAO exhibited stable rotational motion when surrounded by Matrigel. We developed a computational framework leveraging computer vision algorithms to quantify AOAO rotation and correlated it with the direct measurement of cilia motility. We further established the feasibility of using AOAO rotation to recapitulate and measure defective cilia motility caused by chemotherapy-induced toxicity and by CCDC39 mutations in cells from patients with primary ciliary dyskinesia. We expect our rotating AOAO model and the associated computational pipeline to offer a generalizable framework to expedite the modeling of and therapeutic development for genetic and environmental ciliopathies.
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