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The AIR model provides a bridge between the current in -vitro and in-vivo models to study the effects of lung injury in 3D lung tissue slices. Here, we show that the AIR model can be adapted for use in human tissue as a translational model for discovery research and drug screening.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>To generate PCLS, resected human lung tissue was coated with alginate hydrogel to form an artificial pleura. Lung tissue was inflated by point injecting 3% agarose, followed by generation of 450\u2013500 \u00b5M thick slices of tissue. An isolated area of each slice was injured by brief application of 0.1\u00a0M hydrochloric acid. AIR-PCLS were then washed and cultured for 48\u00a0h before immunostaining to assess proliferating cells (Ki67) alveolar type II\/progenitor cell markers (HTII, proSP-C), lipofibroblasts (ADRP) and endothelial cells (ERG). Viability of PCLS was assessed by both MTT assay and Live\/Dead staining.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>We show that levels of proliferation do not change in response to acid injury. However, there is a significant increase in the percentage of proSP-C and HTII positive cells in the injured regions of AIR-PCLS. We also identify non-epithelial cell populations; lipofibroblasts and endothelial cells in human AIR-PCLS, to demonstrate that other repair relevant cell types can be identified and tracked in the human AIR (hAIR model).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>The hAIR model is an effective ex-vivo tool to study early mechanisms of lung repair following injury. By establishing an area of injured tissue adjacent to uninjured tissue, this model mimics the heterogenous pattern of lung injury frequently present in lung diseases. The hAIR model will facilitate mechanistic studies of human lung repair and provides a valuable pre-clinical model for drug testing.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s12931-025-03314-6","type":"journal-article","created":{"date-parts":[[2025,7,5]],"date-time":"2025-07-05T04:50:59Z","timestamp":1751691059000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A human PCLS model of lung injury and repair for discovery and pharmaceutical research"],"prefix":"10.1186","volume":"26","author":[{"given":"Esther","family":"Bankole","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chun Wai","family":"Wong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sally","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew","family":"Hind","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charlotte H.","family":"Dean","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,7,5]]},"reference":[{"issue":"1","key":"3314_CR1","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1016\/j.devcel.2021.11.007","volume":"57","author":"X Sun","year":"2022","unstructured":"Sun X, Perl AK, Li R, Bell SM, Sajti E, Kalinichenko VV, et al. 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Lung tissue samples were collected from patients undergoing lung resection at the Royal Brompton & Harefield hospital (RBHT), by Biobank sample co-ordinators within the RBHT Clinical Research Facility. All samples were obtained following informed consent from patients. The research was conducted under the RBHT Biobank ethics reference number: 20\/SC\/0142 (Supplemental Table ).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"237"}}