title: Aerosol-based airway epithelial cell delivery improves airway regeneration and repair.
abstract: Aerosol-based cell therapy has emerged as a novel and promising therapeutic strategy for treating lung diseases. The goal of this study was to determine the safety and efficacy of aerosol-based airway epithelial cell (AEC) delivery in the setting of acute lung injury induced by tracheal brushing in rabbit. Twenty-four hours following injury, exogenous rabbit AECs were labelled with bromodeoxyuridine and aerosolized using the MicroSprayer® Aerosolizer into the injured airway. Histopathological assessments of the injury in the trachea and lungs were quantitatively scored (1 and 5 days after cell delivery). The aerosol-based AEC delivery appeared to be a safe procedure, as cellular rejection and complications in the liver and spleen were not detected. Airway injury initiated by tracheal brushing resulted in disruption of the tracheal epithelium as well as morphological damage in the lungs that is consistent with acute lung injury. Lung injury scores were reduced following 5 days after AEC delivery (AEC-treated, 0.25  ±  0.06 vs. untreated, 0.53  ±  0.05, P  <  0.01), and rapid clearance of haemorrhage, proteinaceous debris and hyaline membranes occurred. In the trachea, AEC delivery led to an upsurge in epithelium regeneration and repair. Re-epithelialization was significantly increased 5 days after treatment (AEC-treated, 91.07  ±  2.37% vs. untreated, 62.99  ±  7.39%, P  <  0.01). Our results indicate that AEC delivery helps in the regeneration and repair of the respiratory airway, including the lungs, following acute insults. These findings suggest that aerosol-based AEC delivery can be a valuable tool for future therapy to treat acute lung injury. Copyright © 2017 John Wiley & Sons, Ltd.
authors.affiliation: Regenerative Medicine Cluster, Advanced Medical and Dental Institute (AMDI), Universiti Sains Malaysia, Kepala Batas, Penang, Malaysia.
authors.forename: E
authors.identifier: 0000-0001-8391-506X
authors.initials: E
authors.lastname: Kardia
authors.affiliation: Oncology and Radiological Sciences Cluster, Advanced Medical and Dental Institute (AMDI), Universiti Sains Malaysia, Kepala Batas, Penang, Malaysia.
authors.forename: E S
authors.initials: ES
authors.lastname: Ch'ng
authors.affiliation: Regenerative Medicine Cluster, Advanced Medical and Dental Institute (AMDI), Universiti Sains Malaysia, Kepala Batas, Penang, Malaysia.
authors.forename: B H
authors.identifier: 0000-0002-3295-9676
authors.initials: BH
authors.lastname: Yahaya
mesh_terms: D055371:Acute Lung Injury / Q000473:pathology / Q000503:physiopathology; D000336:Aerosols / Q000494:pharmacology*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D004847:Epithelial Cells / Q000166:cytology / Q000637:transplantation*; D005260:Female; D008168:Lung / Q000473:pathology* / Q000503:physiopathology*; D008297:Male; D011817:Rabbits; D012038:Regeneration / Q000187:drug effects; D014132:Trachea / Q000187:drug effects / Q000293:injuries / Q000473:pathology / Q000503:physiopathology; D014945:Wound Healing / Q000187:drug effects
chemical_list: D000336:Aerosols
keywords: acute lung injury; aerosol-based cell delivery; airway epithelial cells; trachea injury; cell therapy; epithelium repair