Modeling pulmonary cystic fibrosis in a human lung airway-on-a-chip.

Autor: Plebani R; Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, United States; Center on Advanced Studies and Technology (CAST), Department of Medical, Oral and Biotechnological Sciences, 'G. d'Annunzio' University of Chieti-Pescara, Chieti, Italy., Potla R; Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, United States; Vascular Biology Program and Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, MA, United States., Soong M; Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, United States., Bai H; Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, United States., Izadifar Z; Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, United States., Jiang A; Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, United States., Travis RN; Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, United States., Belgur C; Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, United States., Dinis A; Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, United States., Cartwright MJ; Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, United States., Prantil-Baun R; Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, United States., Jolly P; Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, United States., Gilpin SE; Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, United States., Romano M; Center on Advanced Studies and Technology (CAST), Department of Medical, Oral and Biotechnological Sciences, 'G. d'Annunzio' University of Chieti-Pescara, Chieti, Italy., Ingber DE; Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, United States; Vascular Biology Program and Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, MA, United States; Harvard John A. Paulson School of Engineering and Applied Sciences, Cambridge, MA, United States. Electronic address: don.ingber@wyss.harvard.edu.
Jazyk: angličtina
Zdroj: Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society [J Cyst Fibros] 2022 Jul; Vol. 21 (4), pp. 606-615. Date of Electronic Publication: 2021 Nov 17.
DOI: 10.1016/j.jcf.2021.10.004
Abstrakt: Background: Cystic fibrosis (CF) is a genetic disease caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR), which results in impaired airway mucociliary clearance, inflammation, infection, and respiratory insufficiency. The development of new therapeutics for CF are limited by the lack of reliable preclinical models that recapitulate the structural, immunological, and bioelectrical features of human CF lungs.
Methods: We leveraged organ-on-a-chip technology to develop a microfluidic device lined by primary human CF bronchial epithelial cells grown under an air-liquid interface and interfaced with pulmonary microvascular endothelial cells (CF Airway Chip) exposed to fluid flow. The responses of CF and healthy Airway Chips were analyzed in the presence or absence of polymorphonuclear leukocytes (PMNs) and the bacterial pathogen, Pseudomonas aeruginosa.
Results: The CF Airway Chip faithfully recapitulated many features of the human CF airways, including enhanced mucus accumulation, increased cilia density, and a higher ciliary beating frequency compared to chips lined by healthy bronchial epithelial cells. The CF chips also secreted higher levels of IL-8, which was accompanied by enhanced PMN adhesion to the endothelium and transmigration into the airway compartment. In addition, CF Airway Chips provided a more favorable environment for Pseudomonas aeruginosa growth, which resulted in enhanced secretion of inflammatory cytokines and recruitment of PMNs to the airway.
Conclusions: The human CF Airway Chip may provide a valuable preclinical tool for pathophysiology studies as well as for drug testing and personalized medicine.
Competing Interests: Declaration of Competing Interest D.E.I. is a founder, board member, scientific advisory board chair, and equity holder in Emulate, Inc.
(Copyright © 2021 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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