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The Acid Injury and Repair (AIR) model: A new ex vivo tool to understand lung repair
File(s)
Author(s)
Kim, Sally Yunsun
Mongey, Sally
Wang, Peizhu
Rothery, Stephen
Gabiriau, David
Type
Journal Article
Abstract
Research into mechanisms underlying lung injury and subsequent repair responses is currently of paramount importance. There is a paucity of models that bridge the gap between in vitro and in vivo research. Such intermediate models are critical for researchers to decipher the mechanisms that drive repair and to test potential new treatments for lung repair and regeneration. Here we report the establishment of a new tool, the Acid Injury and Repair (AIR) model, that will facilitate studies of lung tissue repair. In this model, injury is applied to a restricted area of a precision-cut lung slice using hydrochloric acid, a clinically relevant driver. The surrounding area remains uninjured, thus mimicking the heterogeneous pattern of injury frequently observed in lung diseases. We show that in response to injury, the percentage of progenitor cells (pro surfactant protein C, proSP-C and TM4SF1 positive) significantly increases in the injured region. Whereas in the uninjured area, the percentage of proSP-C/TM4SF1 cells remains unchanged but proliferating cells (Ki67 positive) increase. These effects are modified in the presence of inhibitors of proliferation (Cytochalasin D) and Wnt secretion (C59) demonstrating that the AIR model is an important new tool for research into lung disease pathogenesis and potential regenerative medicine strategies.
Date Issued
2021-01-01
Date Acceptance
2020-10-18
Citation
Biomaterials, 2021, 267
URI
DOI
ISSN
0142-9612
Publisher
Elsevier
Journal / Book Title
Biomaterials
Volume
267
Copyright Statement
© 2020 Elsevier Ltd. All rights reserved. This manuscript is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Licence http://creativecommons.org/licenses/by-nc-nd/4.0/
License URL
Sponsor
Royal Brompton & Harefield NHS Foundation Trust
Royal Brompton & Harefield Hospitals Charity
Wellcome Trust
Grant Number
B1064
B1064
104931/Z/14/Z
Subjects
Acid injury
Ex-vivo model
Lung injury
Precision-cut lung slices
Tissue repair
lung progenitors
Biomedical Engineering
Publication Status
Published
Article Number
ARTN 120493
Date Publish Online
2020-10-21