An ex vivo model to induce early fibrosis-like changes in human precision-cut lung slices
Open accessAbstract
Idiopathic pulmonary fibrosis (IPF) is a devastating chronic interstitial lung disease (ILD) characterized by lung tissue scarring and high morbidity. Lung epithelial injury, myofibroblast activation, and deranged repair are believed to be key processes involved in disease onset and progression, but the exact molecular mechanisms behind IPF remain unclear. Several drugs have been shown to slow disease progression, but treatments that halt or reverse IPF progression have not been identified. Ex vivo models of human lung have been proposed for drug discovery, one of which is precision-cut lung slices (PCLS). Although PCLS production from IPF explants is possible, IPF explants are rare and typically represent end-stage disease. Here we present a novel model of early fibrosis-like changes in human PCLS derived from patients without ILD/IPF using a combination of profibrotic growth factors and signaling molecules (transforming growth factor-β, tumor necrosis factor-α, platelet-derived growth factor-AB, and lysophosphatidic acid). Fibrotic-like changes of PCLS were qualitatively analyzed by histology and immunofluorescence and quantitatively by water-soluble tetrazolium-1, RT-qPCR, Western blot analysis, and ELISA. PCLS remained viable after 5 days of treatment, and fibrotic gene expression ( FN1, SERPINE1, COL1A1, CTGF, MMP7, and ACTA2) increased as early as 24 h of treatment, with increases in protein levels at 48 h and increased deposition of extracellular matrix. Alveolar epithelium reprogramming was evident by decreases in surfactant protein C and loss of HOPX. In summary, using human-derived PCLS, we established a novel ex vivo model that displays characteristics of early fibrosis and could be used to evaluate novel therapies and study early-stage IPF pathomechanisms.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
It is now possible to induce several features mimicking the fibrogenic response by applying a profibrotic cytokine cocktail (e.g. TGFβ1, LPA, and IL-1) in PCLS obtained from control tissue over the course of a few days.
“it is now possible to induce several features which mimic the fibrogenic response by applying a profibrotic cytokine cocktail (e.g. TGFβ1, lysophosphatidic acid receptor (LPA), and interleukin-1 (IL-1)), in PCLS obtained from control tissue over the course of a few days (Alsafadi et al., 2017).”
From Pulmonary fibrosis: Emerging diagnostic and therapeutic strategies (2023) · cites this paper as Alsafadi et al., 2017
Cites
King, T. E., Pardo, A., & Selman, M. (2011) · The Lancet · doi:10.1016/s0140-6736(11)60052-4 · Cited by 2,194 · see citing works
Murine models of pulmonary fibrosis
Moore, B. B., & Hogaboam, C. M. (2007) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00313.2007 · Cited by 797 · see citing works
Booth, A. J., Hadley, R., Cornett, A. M., Dreffs, A. A., Matthes, S. A., Tsui, J. L., Weiss, K., Horowitz, J. C., Fiore, V. F., Barker, T. H., et al. (2012) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201204-0754oc · Cited by 665 · see citing works
Increased stiffness of the rat liver precedes matrix deposition: implications for fibrosis
Georges, P. C., Hui, J.-J., Gombos, Z., McCormick, M. E., Wang, A. Y., Uemura, M., Mick, R., Janmey, P. A., Furth, E. E., & Wells, R. G. (2007) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00032.2007 · Cited by 577 · see citing works
Xu, Y. J., Mizuno, T., Sridharan, A., Du, Y., Guo, M., Tang, J., Wikenheiser‐Brokamp, K. A., Perl, A. T., Funari, V. A., Gokey, J. J., et al. (2016) · JCI Insight · doi:10.1172/jci.insight.90558 · Cited by 571 · see citing works
Role of Epithelial Cells in Idiopathic Pulmonary Fibrosis: From Innocent Targets to Serial Killers
Selman, M., & Pardo, A. (2006) · Proceedings of the American Thoracic Society · doi:10.1513/pats.200601-003tk · Cited by 528 · see citing works
Arora, P. D., Narani, N., & McCulloch, C. A. (1999) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)65334-5 · Cited by 465 · see citing works
Plasticity of Hopx(+) type I alveolar cells to regenerate type II cells in the lung
Jain, R., Barkauskas, C. E., Takeda, N., Bowie, E. J., Aghajanian, H., Wang, Q., Padmanabhan, A., Manderfield, L. J., Gupta, M., Li, D., et al. (2015) · Nature Communications · doi:10.1038/ncomms7727 · Cited by 303 · see citing works
WNT5A Is a Regulator of Fibroblast Proliferation and Resistance to Apoptosis
Vuga, L. J., Ben‐Yehudah, A., Kovkarova-Naumovski, E., Oriss, T. B., Gibson, K. F., Feghali‐Bostwick, C. A., & Kaminski, N. (2009) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2008-0201oc · Cited by 215 · see citing works
Exploration of a potent PI3 kinase/mTOR inhibitor as a novel anti-fibrotic agent in IPF
Mercer, P. F., Woodcock, H. V., Eley, J. D., Platé, M., Sulikowski, M. G., Durrenberger, P. F., Franklin, L., Nanthakumar, C. B., Man, Y., Genovese, F., et al. (2016) · Thorax · doi:10.1136/thoraxjnl-2015-207429 · Cited by 206 · see citing works
Chemokine/Cytokine Cocktail in Idiopathic Pulmonary Fibrosis
Agostini, C., & Gurrieri, C. (2006) · Proceedings of the American Thoracic Society · doi:10.1513/pats.200601-010tk · Cited by 196 · see citing works
WNT/β-Catenin Signaling Induces IL-1β Expression by Alveolar Epithelial Cells in Pulmonary Fibrosis
Aumiller, V., Balsara, N., Wilhelm, J., Günther, A., & Königshoff, M. (2013) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2012-0524oc · Cited by 183 · see citing works
Self-citationRaghu, G., & Selman, M. (2015) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201411-2044ed · Cited by 180 · see citing works
White, E. S., Xia, M., Murray, S., Dyal, R., Flaherty, C. M., Flaherty, K. R., Moore, B. B., Cheng, L., Doyle, T. J., Villalba, J., et al. (2016) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201505-0862oc · Cited by 180 · see citing works
Preclinical validation and imaging of Wnt-induced repair in human 3D lung tissue cultures
Uhl, F. E., Vierkotten, S., Wagner, D. E., Burgstaller, G., Costa, R., Koch, I., Lindner, M., Meiners, S., Eickelberg, O., & Königshoff, M. (2015) · European Respiratory Journal · doi:10.1183/09031936.00183214 · Cited by 165 · see citing works
Self-citationMarinković, А., Mih, J. D., Park, J., Liu, F., & Tschumperlin, D. J. (2012) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00108.2012 · Cited by 143 · see citing works
Wagner, D. E., Bonenfant, N. R., Sokocevic, D., DeSarno, M., Borg, Z. D., Parsons, C. S., Brooks, E. M., Platz, J. J., Khalpey, Z. I., Hoganson, D. M., et al. (2014) · Biomaterials · doi:10.1016/j.biomaterials.2013.11.078 · Cited by 140 · see citing works
Self-citationAssessment of immunotoxicity induced by chemicals in human precision-cut lung slices (PCLS)
Lauenstein, L., Switalla, S., Prenzler, F., Seehase, S., Pfennig, O., Förster, C., Fieguth, H., Braun, A. C., & Sewald, K. (2014) · Toxicology in Vitro · doi:10.1016/j.tiv.2013.12.016 · Cited by 78 · see citing works
Martin, C., Uhlig, S., & Ullrich, V. (2001) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/ajrcmb.24.2.3545 · Cited by 64 · see citing works
Tatler, A. L., Barnes, J. L., Habgood, A., Goodwin, A. T., McAnulty, R. J., & Jenkins, G. R. (2016) · Thorax · doi:10.1136/thoraxjnl-2015-208215 · Cited by 62 · see citing works
Rydell‐Törmänen, K., Zhou, X.-H., Hällgren, O., Einarsson, J., Eriksson, L. T., Andersson‐Sjöland, A., & Westergren‐Thorsson, G. (2016) · Physiological Reports · doi:10.14814/phy2.12727 · Cited by 30 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Shared and distinct mechanisms of fibrosis
Distler, J. H. W., Györfi, A., Ramanujam, M., Whitfield, M. L., Königshoff, M., & Lafyatis, R. (2019) · Nature Reviews Rheumatology · doi:10.1038/s41584-019-0322-7 · Cited by 645 · see citing works
Self-citationLehmann, M., Korfei, M., Mutze, K., Klee, S., Skronska-Wasek, W., Alsafadi, H. N., Ota, C., Costa, R., Schiller, H. B., Lindner, M., et al. (2017) · European Respiratory Journal · doi:10.1183/13993003.02367-2016 · Cited by 403 · see citing works
Self-citationUse of precision cut lung slices as a translational model for the study of lung biology
Liu, G., Betts, C., Cunoosamy, D. M., Åberg, P. M., Hornberg, J. J., Sivars, K. B., & Cohen, T. S. (2019) · Respiratory Research · doi:10.1186/s12931-019-1131-x · Cited by 206 · see citing works
The WNT signaling pathways in wound healing and fibrosis
Burgy, O., & Königshoff, M. (2018) · Matrix Biology · doi:10.1016/j.matbio.2018.03.017 · Cited by 182 · see citing works
Self-citationIncreased Extracellular Vesicles Mediate WNT5A Signaling in Idiopathic Pulmonary Fibrosis
Martín-Medina, A., Lehmann, M., Burgy, O., Hermann, S., Baarsma, H. A., Wagner, D. E., Santis, M. M. D., Ciolek, F., Hofer, T. P. J., Frankenberger, M., et al. (2018) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201708-1580oc · Cited by 183 · see citing works
Self-citationRusso, B. F., Brembilla, N. C., & Chizzolini, C. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00648 · Cited by 177 · see citing works
Pathology and pathobiology of pulmonary hypertension: current insights and future directions
Guignabert, C., Aman, J., Bonnet, S., Dorfmüller, P., Olschewski, A., Pullamsetti, S. S., Rabinovitch, M., SCHERMULY, R. T., Humbert, M. J. C., & Stenmark, K. R. (2024) · European Respiratory Journal · doi:10.1183/13993003.01095-2024 · Cited by 178 · see citing works
Spray drying siRNA-lipid nanoparticles for dry powder pulmonary delivery
Zimmermann, C. M., Baldassi, D., Chan, K. Y. T., Adams, N. B. P., Neumann, A., Porras-Gonzalez, D., Wei, X. C., Kneidinger, N., Stoleriu, M. G., Burgstaller, G., et al. (2022) · Journal of Controlled Release · doi:10.1016/j.jconrel.2022.09.021 · Cited by 153 · see citing works
Lignelli, E., Palumbo, F., Myti, D., & Morty, R. E. (2019) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00369.2019 · Cited by 151 · see citing works
Pharmacotherapy and adjunctive treatment for idiopathic pulmonary fibrosis (IPF)
Saito, S., Alkhatib, A. L., Kolls, J. K., Kondoh, Y., & Lasky, J. A. (2019) · Journal of Thoracic Disease · doi:10.21037/jtd.2019.04.62 · Cited by 148 · see citing works
Alsafadi, H. N., Uhl, F. E., Pineda, R., Bailey, K. E., Rojas, M. M., Wagner, D. E., & Königshoff, M. (2020) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2019-0276tr · Cited by 145 · see citing works
Self-citationLehmann, M., Buhl, L., Alsafadi, H. N., Klee, S., Hermann, S., Mutze, K., Ota, C., Lindner, M., Behr, J., Hilgendorff, A., et al. (2018) · Respiratory Research · doi:10.1186/s12931-018-0876-y · Cited by 136 · see citing works
Self-citationA lung targeted miR-29 mimic as a therapy for pulmonary fibrosis
Chioccioli, M., Roy, S., Newell, R., Pestano, L., Dickinson, B., Rigby, K., Herazo-Maya, J., Jenkins, G., Ian, S., Saini, G., et al. (2022) · eBioMedicine · doi:10.1016/j.ebiom.2022.104304 · Cited by 129 · see citing works
Ahangari, F., Becker, C., Foster, D. G., Chioccioli, M., Nelson, M., Beke, K. M., Wang, X., Justet, A., Adams, T. S., Readhead, B. P., et al. (2022) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.202010-3832oc · Cited by 116 · see citing works
Benjamin, J. T., Plosa, E. J., Sucre, J. M. S., van der Meer, R., Dave, S., Gutor, S. S., Nichols, D. S., Gulleman, P. M., Jetter, C. S., Han, W., et al. (2020) · Journal of Clinical Investigation · doi:10.1172/jci139481 · Cited by 96 · see citing works
Novel drug delivery systems and disease models for pulmonary fibrosis
Li, R., Jia, Y., Kong, X., Nie, Y., Deng, Y., & Liu, Y. (2022) · Journal of Controlled Release · doi:10.1016/j.jconrel.2022.05.039 · Cited by 93 · see citing works
Dual inhibition of αvβ6 and αvβ1 reduces fibrogenesis in lung tissue explants from patients with IPF
Decaris, M. L., Schaub, J. R., Chen, C., Cha, J., Lee, G. G., Rexhepaj, M., Ho, S. S., Rao, V., Marlow, M. M., Kotak, P., et al. (2021) · Respiratory Research · doi:10.1186/s12931-021-01863-0 · Cited by 94 · see citing works
Precision‐cut lung slices: A powerful ex vivo model to investigate respiratory infectious diseases
Viana, F., O’Kane, C. M., & Schroeder, G. N. (2021) · Molecular Microbiology · doi:10.1111/mmi.14817 · Cited by 92 · see citing works
Bioengineered 3D Models to Recapitulate Tissue Fibrosis
Sacchi, M., Bansal, R., & Rouwkema, J. (2020) · Trends in biotechnology · doi:10.1016/j.tibtech.2019.12.010 · Cited by 91 · see citing works
Lung regeneration: a tale of mice and men
Basil, M. C., & Morrisey, E. E. (2019) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2019.11.006 · Cited by 87 · see citing works
Rindlisbacher, B., Schmid, C., Geiser, T., Bovet, C., & Funke-Chambour, M. (2018) · Respiratory Research · doi:10.1186/s12931-018-0714-2 · Cited by 85 · see citing works
Lang, N. J., Gote-Schniering, J., Porras-Gonzalez, D., Yang, L., Sadeleer, L. D., Jentzsch, R. C., Shitov, V. A., Zhou, S., Ansari, M., Agami, A., et al. (2023) · Science Translational Medicine · doi:10.1126/scitranslmed.adh0908 · Cited by 88 · see citing works
Self-citationRubio, K., Singh, I., Dobersch, S., Sarvari, P., Günther, S., Cordero, J., Mehta, A., Wujak, L. A., Cabrera-Fuentes, H. A., Chao, C., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-10066-7 · Cited by 83 · see citing works
Human Pulmonary 3D Models For Translational Research
Zscheppang, K., Berg, J., Hedtrich, S., Verheyen, L., Wagner, D. E., Suttorp, N., Hippenstiel, S., & Hocke, A. C. (2017) · Biotechnology Journal · doi:10.1002/biot.201700341 · Cited by 76 · see citing works
Self-citationHyperoxia Injury in the Developing Lung Is Mediated by Mesenchymal Expression of Wnt5A
Sucre, J. M. S., Vickers, K. C., Benjamin, J. T., Plosa, E. J., Jetter, C. S., Cutrone, A. M., Ransom, M. A., Anderson, Z. G., Sheng, Q., Fensterheim, B. A., et al. (2020) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201908-1513oc · Cited by 74 · see citing works
Self-citationAhangari, F., Price, N. L., Malik, S., Chioccioli, M., Bärnthaler, T., Adams, T. S., Kim, J., Pradeep, S. P., Ding, S., Cosmos, C., et al. (2023) · JCI Insight · doi:10.1172/jci.insight.158100 · Cited by 70 · see citing works
Ambike, S. S., Cheng, C., Feuerherd, M., Velkov, S., Baldassi, D., Afridi, S. Q., Porras-Gonzalez, D., Wei, X. C., Hagen, P., Kneidinger, N., et al. (2021) · Nucleic Acids Research · doi:10.1093/nar/gkab1248 · Cited by 66 · see citing works
Koziol‐White, C. J., Gebski, E. B., Cao, G., & Panettieri, R. A. (2024) · Respiratory Research · doi:10.1186/s12931-024-02855-6 · Cited by 67 · see citing works
Current models of pulmonary fibrosis for future drug discovery efforts
Yanagihara, T., Chong, S. G., Vierhout, M., Hirota, J. A., Ask, K., & Kolb, M. R. J. (2020) · Expert Opinion on Drug Discovery · doi:10.1080/17460441.2020.1755252 · Cited by 67 · see citing works
Human Lung Organoids—A Novel Experimental and Precision Medicine Approach
Kühl, L., Graichen, P., von Daacke, N., Mende, A., Wygrecka, M., Potaczek, D. P., Miethe, S., & Garn, H. (2023) · Cells · doi:10.3390/cells12162067 · Cited by 66 · see citing works
Harnessing organs-on-a-chip to model tissue regeneration
Tavakol, D. N., Fleischer, S., & Vunjak‐Novakovic, G. (2021) · Cell stem cell · doi:10.1016/j.stem.2021.05.008 · Cited by 66 · see citing works
Lung repair and regeneration: Advanced models and insights into human disease
Basil, M. C., Alysandratos, K., Kotton, D. N., & Morrisey, E. E. (2024) · Cell stem cell · doi:10.1016/j.stem.2024.02.009 · Cited by 64 · see citing works
Doryab, A., Taş, S., Taskin, M. B., Yang, L., Hilgendorff, A., Gröll, J., Wagner, D. E., & Schmid, O. (2019) · Advanced Functional Materials · doi:10.1002/adfm.201903114 · Cited by 63 · see citing works
Self-citationBailey, K. E., Pino, C. J., Lennon, M. L., Lyons, A. C., Jacot, J. G., Lammers, S. R., Königshoff, M., & Magin, C. M. (2019) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2019-0232ma · Cited by 61 · see citing works
Self-citationTargeting Alveolar Repair in Idiopathic Pulmonary Fibrosis
Ptasinski, V., Stegmayr, J., Belvisi, M. G., Wagner, D. E., & Murray, L. A. (2021) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2020-0476tr · Cited by 59 · see citing works
Self-citationThe Challenge of Long-Term Cultivation of Human Precision-Cut Lung Slices
Preuß, E. B., Schubert, S., Werlein, C., Stark, H., Braubach, P., Höfer, A., Plucinski, E. K., Shah, H., Geffers, R., Sewald, K., et al. (2021) · American Journal Of Pathology · doi:10.1016/j.ajpath.2021.10.020 · Cited by 59 · see citing works
Pulmonary fibrosis: Emerging diagnostic and therapeutic strategies
Selvarajah, B., Platé, M., & Chambers, R. C. (2023) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2023.101227 · Cited by 57 · see citing works
Jürgens, D. C., Deßloch, L., Porras-Gonzalez, D., Winkeljann, J., Zielinski, S., Munschauer, M., Hörner, A., Burgstaller, G., Winkeljann, B., & Merkel, O. M. (2023) · OpenNano · doi:10.1016/j.onano.2023.100161 · Cited by 56 · see citing works
What have we learned from basic science studies on idiopathic pulmonary fibrosis?
Yanagihara, T., Sato, S., Upagupta, C., & Kolb, M. R. J. (2019) · European Respiratory Review · doi:10.1183/16000617.0029-2019 · Cited by 54 · see citing works
Kiener, M., Roldán, N., Machahua, C., Sengupta, A., Geiser, T., Guenat, O. T., Funke-Chambour, M., Hobi, N., & Julio, M. K. (2021) · Frontiers in Medicine · doi:10.3389/fmed.2021.644678 · Cited by 52 · see citing works
The Antifibrotic Activity of Prostacyclin Receptor Agonism Is Mediated through Inhibition of YAP/TAZ
Zmajkovicova, K., Menyhart, K., Bauer, Y., Studer, R. O., Renault, B., Schnoebelen, M., Bolinger, M., Nayler, O., & Gatfield, J. (2018) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2018-0142oc · Cited by 52 · see citing works
Ji, J., Zheng, S., Liu, Y., Xie, T., Zhu, X., Nie, Y., Shen, Y., & Han, X. (2023) · Journal of Translational Medicine · doi:10.1186/s12967-023-04279-0 · Cited by 51 · see citing works
The evolution ofin vitromodels of lung fibrosis: promising prospects for drug discovery
Kolanko, E., Cargnoni, A., Papait, A., Silini, A. R., Czekaj, P., & Parolini, O. (2024) · European Respiratory Review · doi:10.1183/16000617.0127-2023 · Cited by 51 · see citing works
Roach, K. M., Sutcliffe, A., Matthews, L., Elliott, G., Newby, C., Amrani, Y., & Bradding, P. H. (2018) · Scientific Reports · doi:10.1038/s41598-017-18555-9 · Cited by 49 · see citing works
Lam, M., Lamanna, E., Organ, L. A., Donovan, C., & Bourke, J. E. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1162889 · Cited by 48 · see citing works
Ota, C., Ng-Blichfeldt, J.-P., Korfei, M., Alsafadi, H. N., Lehmann, M., Skrońska-Wąsek, W., Santis, M. M. D., Günther, A., Wagner, D. E., & Königshoff, M. (2018) · Scientific Reports · doi:10.1038/s41598-018-31214-x · Cited by 49 · see citing works
Self-citationPham, T. X., Lee, J., Guan, J., Caporarello, N., Meridew, J. A., Jones, D. L., Tan, Q., Huang, S. K., Tschumperlin, D. J., & Ligresti, G. (2022) · JCI Insight · doi:10.1172/jci.insight.153672 · Cited by 47 · see citing works
Inhibition of SARS-CoV-2 replication in the lung with siRNA/VIPER polyplexes
Baldassi, D., Ambike, S. S., Feuerherd, M., Cheng, C., Peeler, D. J., Feldmann, D. P., Porras-Gonzalez, D., Wei, X. C., Keller, L.-A., Kneidinger, N., et al. (2022) · Journal of Controlled Release · doi:10.1016/j.jconrel.2022.03.051 · Cited by 47 · see citing works
Ayaub, E., Poli, S., Ng, J., Adams, T. S., Schupp, J. C., Quesada-Arias, L. D., Poli, F., Cosme, C., Robertson, M. J., Manzano, J. M. M., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.01.04.425268 · Cited by 46 · see citing works
Generation of Human 3D Lung Tissue Cultures (3D-LTCs) for Disease Modeling
Gerckens, M., Alsafadi, H. N., Wagner, D. E., Lindner, M., Burgstaller, G., & Königshoff, M. (2019) · Journal of Visualized Experiments · doi:10.3791/58437 · Cited by 44 · see citing works
Self-citationLung regeneration: implications of the diseased niche and ageing
Melo-Narváez, M. C., Stegmayr, J., Wagner, D. E., & Lehmann, M. (2020) · European Respiratory Review · doi:10.1183/16000617.0222-2020 · Cited by 43 · see citing works
Self-citationKhan, M. M., Poeckel, D., Halavatyi, A. A., Zukowska, J., Stein, F., Vappiani, J., Sévin, D. C., Tischer, C., Zinn, N., Eley, J. D., et al. (2020) · European Respiratory Journal · doi:10.1183/13993003.00221-2020 · Cited by 42 · see citing works
Update in Pulmonary Fibrosis 2018
Sgalla, G., Kulkarni, T., Antin-Ozerkis, D. E., Thannickal, V. J., & Richeldi, L. (2019) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201903-0542up · Cited by 42 · see citing works
Lehmann, M., Krishnan, R., Sucre, J. M. S., Kulkarni, H. S., Pineda, R., Anderson, C., Banovich, N. E., Behrsing, H. P., Dean, C. H., Haak, A. J., et al. (2024) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2024-0479st · Cited by 45 · see citing works
Self-citationBigaeva, E., Gore, E., Simon, E., Zwick, M., Oldenburger, A., de Jong, K. P., Hofker, H. S., Schlepütz, M., Nicklin, P. L., Boersema, M., et al. (2019) · Archives of Toxicology · doi:10.1007/s00204-019-02611-6 · Cited by 41 · see citing works
Histological signatures map anti-fibrotic factors in mouse and human lungs
Guo, J. L., Griffin, M., Yoon, J.-K., Lopez, D. M., Zhu, Y., Lu, J. M., Mikos, G., Parker, J. B. L., Mascharak, S., Brenac, C., et al. (2025) · Nature · doi:10.1038/s41586-025-08727-3 · Cited by 41 · see citing works
GPCR-induced YAP activation sensitizes fibroblasts to profibrotic activity of TGFβ1
Zmajkovicova, K., Bauer, Y., Menyhart, K., Schnoebelen, M., Freti, D., Boucher, M., Renault, B., Studer, R. O., Birker, M., Klenk, A., et al. (2020) · PLoS ONE · doi:10.1371/journal.pone.0228195 · Cited by 39 · see citing works
Evaluation of Pirfenidone and Nintedanib in a Human Lung Model of Fibrogenesis
Roach, K., Castells, E., Dixon, K., Mason, S., Elliott, G., Marshall, H., Poblocka, M., Macip, S., Richardson, M., Khalfaoui, L., et al. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.679388 · Cited by 39 · see citing works
Gerckens, M., Schorpp, K., Pelizza, F., Wögrath, M., Reichau, K., Ma, H., Dworsky, A.-M., Sengupta, A., Stoleriu, M. G., Heinzelmann, K., et al. (2021) · Science Advances · doi:10.1126/sciadv.abb3673 · Cited by 36 · see citing works
Self-citationCedilak, M., Banjanac, M., Belamarić, D., Radičević, A. P., Faraho, I., Ilić, K., Čužić, S., Glojnarić, I., Haber, V. E., & Bosnar, M. (2019) · Pulmonary Pharmacology & Therapeutics · doi:10.1016/j.pupt.2019.02.005 · Cited by 38 · see citing works
Burgstaller, G., Sengupta, A., Vierkotten, S., Preißler, G., Lindner, M., Behr, J., Königshoff, M., & Eickelberg, O. (2018) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00408.2017 · Cited by 36 · see citing works
Self-citationThe Role of Pulmonary Surfactant Phospholipids in Fibrotic Lung Diseases
Tlatelpa-Romero, B., Cázares‐Ordoñez, V., Oyarzábal, L. F., & Cisneros, L. G. V.-D.-L. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms24010326 · Cited by 36 · see citing works
Epithelial stem cells and niches in lung alveolar regeneration and diseases
Zhang, J., & Liu, Y. (2024) · Chinese Medical Journal - Pulmonary and Critical Care Medicine · doi:10.1016/j.pccm.2023.10.007 · Cited by 35 · see citing works
Zheng, Y., Schupp, J. C., Adams, T. S., Clair, G., Justet, A., Ahangari, F., Yan, X., Hansen, P., Carlon, M. S., Cortesi, E. E., et al. (2025) · Nature Biomedical Engineering · doi:10.1038/s41551-025-01423-7 · Cited by 38 · see citing works
Self-citationWagner, D. E., Alsafadi, H. N., Mitash, N., Justet, A., Hu, Q., Pineda, R., Staab-Weijnitz, C. A., Korfei, M., Gvazava, N., Wannemo, K., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-61795-x · Cited by 33 · see citing works
Self-citationVazquez‐Armendariz, A. I., Barroso, M. M., Agha, E. E., & Herold, S. (2022) · Cells · doi:10.3390/cells11091526 · Cited by 35 · see citing works
Preserving Airway Smooth Muscle Contraction in Precision-Cut Lung Slices
Li, G., Cohen, J. A., Martines, C. M., Ram‐Mohan, S., Brain, J. D., Krishnan, R., Ai, X., & Bai, Y. (2020) · Scientific Reports · doi:10.1038/s41598-020-63225-y · Cited by 32 · see citing works
Modeling fibrotic alveolar transitional cells with pluripotent stem cell-derived alveolar organoids
Ptasinski, V., Monkley, S. J., Öst, K., Tammia, M., Alsafadi, H. N., Overed-Sayer, C. L., Hazon, P., Wagner, D. E., & Murray, L. A. (2023) · Life Science Alliance · doi:10.26508/lsa.202201853 · Cited by 34 · see citing works
Self-citationHuang, Q., Chen, Y., Shen, S., Wang, Y., Liu, L., Wu, S., Xu, W. D., Zhao, W., Lin, M., & Wu, J. (2020) · Aging · doi:10.18632/aging.102978 · Cited by 31 · see citing works
Patel, V., Amin, K., Wahab, A., Marimoutou, M., Ukishima, L., Alvarez, J., Battle, K., Stucki, A., Clippinger, A. J., & Behrsing, H. P. (2023) · Toxicological Sciences · doi:10.1093/toxsci/kfac136 · Cited by 29 · see citing works
Tissue-informed engineering strategies for modeling human pulmonary diseases
Bailey, K. E., Floren, M. L., D’Ovidio, T. J., Lammers, S. R., Stenmark, K. R., & Magin, C. M. (2018) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00353.2018 · Cited by 29 · see citing works
Nizamoglu, M., Joglekar, M. M., Almeida, C. R., Larsson‐Callerfelt, A., Dupin, I., Guenat, O. T., Henrot, P., van Os, L., Otero, J., Elowsson, L., et al. (2023) · European Respiratory Review · doi:10.1183/16000617.0042-2023 · Cited by 28 · see citing works
Jiménez-Valdés, R. J., Can, U. I., Niemeyer, B. F., & Benam, K. H. (2020) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2020.00989 · Cited by 27 · see citing works
Akinbote, A., Beltrán-Sastre, V., Cherubini, M., Visone, R., Hajal, C., Cobanoglu, D., & Haase, K. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.735915 · Cited by 27 · see citing works
Gvazava, N., Konings, S. C., Cepeda-Prado, E., Skoryk, V. R., Umeano, C. H., Dong, J., Silva, I. A. N., Ottosson, D. R., Leigh, N. D., Wagner, D. E., et al. (2023) · Journal of the American Chemical Society · doi:10.1021/jacs.3c08854 · Cited by 26 · see citing works
Self-citationStem cell migration drives lung repair in living mice
Chioccioli, M., Liu, S., Magruder, S., Tata, A., Borriello, L., McDonough, J. E., Konkimalla, A., Kim, S., Nouws, J., Gonzalez, D. G., et al. (2024) · Developmental Cell · doi:10.1016/j.devcel.2024.02.003 · Cited by 26 · see citing works
The Use of Precision‐Cut Lung Slices for Studying Innate Immunity to Viral Infections
Michalaki, C., Dean, C. H., & Johansson, C. (2022) · Current Protocols · doi:10.1002/cpz1.505 · Cited by 26 · see citing works
Banerjee, S. K., Huckuntod, S. D., Mills, S. D., Kurten, R. C., & Pechous, R. D. (2019) · Infection and Immunity · doi:10.1128/iai.00175-19 · Cited by 25 · see citing works
Fatty acid nitroalkene reversal of established lung fibrosis
Koudelka, A., Cechova, V., Rojas, M. M., Mitash, N., Bondonese, A., Croix, C. M. S., Ross, M. A., & Freeman, B. Α. (2021) · Redox Biology · doi:10.1016/j.redox.2021.102226 · Cited by 25 · see citing works
Three-dimensional models of the lung: past, present and future: a mini review
Sen, C., Freund, D., & Gomperts, B. N. (2022) · Biochemical Society Transactions · doi:10.1042/bst20190569 · Cited by 23 · see citing works
Huang, X., Cai, H., Ammar, R., Zhang, Y., Wang, Y., Ravi, K., Thompson, J. R., & Járai, G. (2018) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00281.2018 · Cited by 24 · see citing works
Extracellular Matrix as a Driver of Chronic Lung Diseases
Burgess, J. K., Weiss, D. J., Westergren‐Thorsson, G., Wigén, J., Dean, C. H., Mumby, S. E., Bush, A., & Adcock, I. M. (2024) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2023-0176ps · Cited by 24 · see citing works
Huang, M., Smith, A., Watson, M. C., Bhandari, R., Baugh, L. M., Ivanovska, I. L., Watkins, T., Lang, I. M., Trojanowska, M. E., Black, L. D., et al. (2022) · Arthritis & Rheumatology · doi:10.1002/art.42097 · Cited by 23 · see citing works
Patel, V., Amin, K., Allen, D., Ukishima, L., Wahab, A., Grodi, C., & Behrsing, H. P. (2021) · Alternatives to Laboratory Animals · doi:10.1177/02611929211061884 · Cited by 22 · see citing works
Liu, Y., Wu, P., Wang, Y., Liu, Y., Yang, H., Zhou, G., Wu, X., & Wen, Q. (2022) · Bioengineering · doi:10.3390/bioengineering9120767 · Cited by 22 · see citing works
Gaudino, M., Lion, A., Sagné, E., Nagamine, B. S., Oliva, J., Terrier, O., Errazuriz-Cerda, E., Scribe, A., Sikht, F., Simon, E. D. S., et al. (2023) · Journal of Virology · doi:10.1128/jvi.01423-22 · Cited by 22 · see citing works
Alveolar repair following LPS-induced injury requires cell-ECM interactions
Sucre, J. M. S., Bock, F. M., Negretti, N. M., Benjamin, J. T., Gulleman, P. M., Dong, X., Ferguson, K. T., Jetter, C. S., Han, W., Liu, Y., et al. (2023) · JCI Insight · doi:10.1172/jci.insight.167211 · Cited by 22 · see citing works
Mouse Lung Tissue Slice Culture
Wu, X., van Dijk, E. M., Bos, I. S. T., Kistemaker, L. E. M., & Gosens, R. (2019) · Methods in molecular biology · doi:10.1007/978-1-4939-9086-3_21 · Cited by 22 · see citing works
Albendazole ameliorates aerobic glycolysis in myofibroblasts to reverse pulmonary fibrosis
Zeng, C., Yue, H., Wang, C., Ju, X., Wang, T., Fu, X., Zhou, Q., Zhang, H., He, L., Yu, J., et al. (2024) · Journal of Translational Medicine · doi:10.1186/s12967-024-05655-0 · Cited by 21 · see citing works
Egea-Zorrilla, A., Vera, L., Sáez, B., & Pardo–Saganta, A. (2022) · Cells · doi:10.3390/cells11162595 · Cited by 20 · see citing works
Human lung virtual histology by multi-scale x-ray phase-contrast computed tomography
Reichmann, J., Verleden, S. E., Kühnel, M., Kamp, J. C., Werlein, C., Neubert, L., Müller, J.-H., Bui, T. Q., Ackermann, M., Jonigk, D. D., et al. (2023) · Physics in Medicine and Biology · doi:10.1088/1361-6560/acd48d · Cited by 20 · see citing works
Yao, Y., Ritzmann, F., Miethe, S., Kattler‐Lackes, K., Colakoglu, B., Herr, C., Kamyschnikow, A., Brand, M., Garn, H., Yildiz, D., et al. (2024) · Molecular Medicine · doi:10.1186/s10020-024-00990-w · Cited by 20 · see citing works
IL-4-induced SOX9 confers lineage plasticity to aged adult lung stem cells
Cai, X. T., Jia, M., Heigl, T., Shamir, E. R., Wong, A. K., Hall, B. M., Arlantico, A., Hung, J., Menon, H. G., Darmanis, S., et al. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.114569 · Cited by 19 · see citing works
Biofabrication: An interesting tool to create in vitro model for COVID-19 drug targets
Singh, A. K., Mishra, G., Maurya, A., Kulkarni, G. T., & Awasthi, R. (2020) · Medical Hypotheses · doi:10.1016/j.mehy.2020.110059 · Cited by 19 · see citing works
Huang, X., Li, L., Ammar, R., Zhang, Y., Wang, Y., Ravi, K., Thompson, J. R., & Járai, G. (2018) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00339.2018 · Cited by 19 · see citing works
Transcriptomic profiling of induced steatosis in human and mouse precision-cut liver slices
Simon, E., Motyka, M., Prins, G. H., Li, M., Rust, W., Kauschke, S. G., Viollet, C., Olinga, P., & Oldenburger, A. (2023) · Scientific Data · doi:10.1038/s41597-023-02220-0 · Cited by 19 · see citing works
Dehydroepiandrosterone in fibrotic interstitial lung disease: a translational study
Guler, S. A., Machahua, C., Geiser, T., Kocher, G. J., Marti, T. M., Tan, B., Trappetti, V., Ryerson, C. J., & Funke-Chambour, M. (2022) · Respiratory Research · doi:10.1186/s12931-022-02076-9 · Cited by 18 · see citing works
Montesi, S. B., Gómez, C. R., Beers, M. F., Brown, R., Chattopadhyay, I., Flaherty, K. R., Garcia, C. K., Gomperts, B. N., Hariri, L. P., Hogaboam, C. M., et al. (2023) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.202307-1154ws · Cited by 18 · see citing works
Self-citationMarchal‐Duval, E., Homps-Legrand, M., Froidure, A., Jaillet, M., Ghanem, M., Deneuville, L., Justet, A., Maurac, A., Vadel, A., Fortas, E., et al. (2023) · eLife · doi:10.7554/elife.79840 · Cited by 18 · see citing works
Tissue traction microscopy to quantify muscle contraction within precision-cut lung slices
Ram‐Mohan, S., Bai, Y., Schaible, N., Ehrlicher, A. J., Cook, D. P., Suki, B., Stoltz, D. A., Solway, J., Ai, X., & Krishnan, R. (2019) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00297.2019 · Cited by 18 · see citing works
- Authors
- Alsafadi, H. N., Staab-Weijnitz, C. A., Lehmann, M., Lindner, M., Peschel, B., Königshoff, M., & Wagner, D. E.
- Affiliations
- Helmholtz Munich (DE)
- Asklepios Fachkliniken München-Gauting (DE)
- Helmholtz Zentrum Munich, Comprehensive Pneumology Center, Member of the German Center for Lung Research, Munich, Germany;
- Corresponding author
- Wagner, Darcy E.
- ORCID
- Venue
- American Journal of Physiology-Lung Cellular and Molecular Physiology
- Publisher
- American Physiological Society
- Published
- 2017-06-01
- Volume
- 312
- Issue
- 6
- Pages
- L896-L902
- ISSN
- 1040-0605 (ISSN-L)
- 1522-1504
- OpenAlex
- W2595866898
- Cited by
- 263
- References
- 21
- Citations by year
- 2026: 25 · 2025: 52 · 2024: 39 · 2023: 41 · 2022: 25 · 2021: 24 · 2020: 19 · 2019: 21 · 2018: 14 · 2017: 3
- FWCI
- 12.79
- Type
- journal article
- Language
- en
- Open access
- Licence
- other-oa
- Locations
- American Journal of Physiology-Lung Cellular and Molecular Physiology (publishedVersion)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Site cant be reached (submittedVersion, other-oa)
- Funders
- American Thoracic Society (ATS)
- Helmholtz Zentrum München GmbH
- Whitaker International Fellows and Scholars Program
- Helmholtz Association
- EC | European Research Council (ERC) (ERC-2010-StG 261302)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Health Sciences › Medicine › Surgery › Transplantation: Methods and Outcomes
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Pulmonary Hypertension Research and Treatments
- Keywords
- idiopathic pulmonary fibrosis, precision-cut lung slices, ex vivo model, fibrosis, TGF-beta, TNF-α, PDGF-AB, lysophosphatidic acid, myofibroblast activation, extracellular matrix deposition, surfactant protein C, HOPX, interstitial lung disease
- MeSH terms
- Aged, Extracellular Matrix, Female, Humans, Lung, Male, Models, Biological, Tissue Survival, Biomarkers, Up-Regulation, Inflammation Mediators, Collagen Type I, Idiopathic Pulmonary Fibrosis, Alveolar Epithelial Cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
