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Small airway-on-a-chip enables analysis of human lung inflammation and drug responses in vitro
Open accessAbstract
Here we describe the development of a human lung 'small airway-on-a-chip' containing a differentiated, mucociliary bronchiolar epithelium and an underlying microvascular endothelium that experiences fluid flow, which allows for analysis of organ-level lung pathophysiology in vitro. Exposure of the epithelium to interleukin-13 (IL-13) reconstituted the goblet cell hyperplasia, cytokine hypersecretion and decreased ciliary function of asthmatics. Small airway chips lined with epithelial cells from individuals with chronic obstructive pulmonary disease recapitulated features of the disease such as selective cytokine hypersecretion, increased neutrophil recruitment and clinical exacerbation by exposure to viral and bacterial infections. With this robust in vitro method for modeling human lung inflammatory disorders, it is possible to detect synergistic effects of lung endothelium and epithelium on cytokine secretion, identify new biomarkers of disease exacerbation and measure responses to anti-inflammatory compounds that inhibit cytokine-induced recruitment of circulating neutrophils under flow.
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Cites
Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT Method
Livak, K. J., & Schmittgen, T. D. (2001) · Methods · doi:10.1006/meth.2001.1262 · Cited by 180,860
Neutrophil recruitment and function in health and inflammation
Kolaczkowska, E., & Kubes, P. (2013) · Nature Reviews Immunology · doi:10.1038/nri3399 · Cited by 5,472
Reconstituting organ-level lung functions on a chip
Huh, D., Matthews, B. D., Mammoto, A., Montoya-Zavala, M., Hsin, H. Y., & Ingber, D. E. (2010) · Science · doi:10.1126/science.1188302 · Cited by 4,250
Self-citationMutation of the mouse klotho gene leads to a syndrome resembling ageing
Kuro-o, M., Matsumura, Y., Aizawa, H., Kawaguchi, H., Suga, T., Utsugi, T., Ohyama, Y., Kurabayashi, M., Kaname, T., Kume, E., et al. (1997) · Nature · doi:10.1038/36285 · Cited by 3,837
Organs-on-chips at the frontiers of drug discovery
Esch, E. W., Bahinski, A., & Huh, D. (2015) · Nature Reviews Drug Discovery · doi:10.1038/nrd4539 · Cited by 1,185
Self-citationInfections and Airway Inflammation in Chronic Obstructive Pulmonary Disease Severe Exacerbations
Papi, A., Bellettato, C. M., Braccioni, F., Romagnoli, M., Casolari, P., Caramori, G., Fabbri, L. M., & Johnston, S. L. (2006) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200506-859oc · Cited by 1,072
Didierlaurent, A., Goulding, J., Patel, S., Snelgrove, R., Low, L., Bebien, M., Lawrence, T., van Rijt, L. S., Lambrecht, B. N., Sirard, J.-C., et al. (2008) · The Journal of Experimental Medicine · doi:10.1084/jem.20070891 · Cited by 399
Cited by
Human organs-on-chips for disease modelling, drug development and personalized medicine
Ingber, D. E. (2022) · Nature Reviews Genetics · doi:10.1038/s41576-022-00466-9 · Cited by 1,589
Self-citationA guide to the organ-on-a-chip
Leung, C. M., de Haan, P., Ronaldson-Bouchard, K., Kim, G.-A., Ko, J., Rho, H. S., Chen, Z., Habibovic, P., Jeon, N. L., Takayama, S., et al. (2022) · Nature Reviews Methods Primers · doi:10.1038/s43586-022-00118-6 · Cited by 1,116
Advances in organ-on-a-chip engineering
Zhang, B., Korolj, A., Lai, B. F. L., & Radisic, M. (2018) · Nature Reviews Materials · doi:10.1038/s41578-018-0034-7 · Cited by 1,017
Modelling cancer in microfluidic human organs-on-chips
Sontheimer-Phelps, A., Hassell, B. A., & Ingber, D. E. (2019) · Nature Reviews Cancer · doi:10.1038/s41568-018-0104-6 · Cited by 906
Self-citationZhang, Y. S., Aleman, J., Shin, S. R., Kilic, T., Kim, D., Mousavi Shaegh, S. A., Massa, S., Riahi, R., Chae, S., Hu, N., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1612906114 · Cited by 833
Vatine, G. D., Barrile, R., Workman, M. J., Sances, S., Barriga, B. K., Rahnama, M., Barthakur, S., Kasendra, M., Lucchesi, C., Kerns, J., et al. (2019) · Cell stem cell · doi:10.1016/j.stem.2019.05.011 · Cited by 632
Self-citationMicrofluidic Organ-on-a-Chip Models of Human Intestine
Bein, A., Shin, W., Jalili-Firoozinezhad, S., Park, M. H., Sontheimer-Phelps, A., Tovaglieri, A., Chalkiadaki, A., Kim, H. J., & Ingber, D. E. (2018) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2017.12.010 · Cited by 625
Self-citationPark, T.-E., Mustafaoglu, N., Herland, A., Hasselkus, R., Mannix, R., FitzGerald, E. A., Prantil-Baun, R., Watters, A., Henry, O., Benz, M., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-10588-0 · Cited by 594
Self-citationScreening out irrelevant cell-based models of disease
Horvath, P., Aulner, N., Bickle, M., Davies, A. M., Nery, E. D., Ebner, D., Montoya, M. C., Östling, P., Pietiäinen, V., Price, L. S., et al. (2016) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.175 · Cited by 525
Organoid-on-a-chip and body-on-a-chip systems for drug screening and disease modeling
Skardal, A., Shupe, T., & Atala, A. (2016) · Drug Discovery Today · doi:10.1016/j.drudis.2016.07.003 · Cited by 512
Henry, O. Y. F., Villenave, R., Cronce, M. J., Leineweber, W. D., Benz, M. A., & Ingber, D. E. (2017) · Lab on a Chip · doi:10.1039/c7lc00155j · Cited by 482
Self-citationHassell, B. A., Goyal, G., Lee, E., Sontheimer-Phelps, A., Levy, O., Chen, C. S., & Ingber, D. E. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.09.043 · Cited by 467
Self-citationSi, L., Bai, H., Rodas, M., Cao, W., Oh, C. Y., Jiang, A., Moller, R., Hoagland, D., Oishi, K., Horiuchi, S., et al. (2021) · Nature Biomedical Engineering · doi:10.1038/s41551-021-00718-9 · Cited by 440
“1b,c) similar to those observed in human airway in vivo 18 , as well as in prior Airway Chip studies that used a membrane with smaller pores that did not permit immune cell transmigration 17 .”
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Zhang, B., & Radisic, M. (2017) · Lab on a Chip · doi:10.1039/c6lc01554a · Cited by 437
Automated microfluidic platform for dynamic and combinatorial drug screening of tumor organoids
Schuster, B., Junkin, M., Kashaf, S. S., Romero-Calvo, I., Kirby, K., Matthews, J., Weber, C. R., Rzhetsky, A., White, K. P., & Tay, S. (2020) · Nature Communications · doi:10.1038/s41467-020-19058-4 · Cited by 424
Jain, A., Barrile, R., van der Meer, A., Mammoto, A., Mammoto, T., De Ceunynck, K., Aisiku, O., Otieno, M., Louden, C., Hamilton, G., et al. (2018) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt.742 · Cited by 325
Self-citationOrgan-on-a-chip platforms: a convergence of advanced materials, cells, and microscale technologies
Ahadian, S., Civitarese, R., Bannerman, D., Mohammadi, M. H., Lu, R., Wang, E., Davenport‐Huyer, L., Lai, B., Zhang, B., Zhao, Y., et al. (2018) · Advanced Healthcare Materials · doi:10.1002/adhm.201700506 · Cited by 315
Benam, K. H., Novak, R., Nawroth, J., Hirano-Kobayashi, M., Ferrante, T. C., Choe, Y., Prantil-Baun, R., Weaver, J. C., Bahinski, A., Parker, K. K., et al. (2016) · Cell Systems · doi:10.1016/j.cels.2016.10.003 · Cited by 309
Self-citationMarx, U. (2016) · ALTEX · doi:10.14573/altex.1603161 · Cited by 295
Bauer, S., Wennberg Huldt, C., Kanebratt, K. P., Durieux, I., Gunne, D., Andersson, S., Ewart, L., Haynes, W. G., Maschmeyer, I., Winter, A., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-14815-w · Cited by 272
Personalised organs-on-chips: functional testing for precision medicine
van den Berg, A., Mummery, C. L., Passier, R., & van der Meer, A. D. (2019) · Lab on a Chip · doi:10.1039/c8lc00827b · Cited by 270
Mimicking liver sinusoidal structures and functions using a 3D-configured microfluidic chip
Du, Y., Li, N., Yang, H., Luo, C., Gong, Y., Tong, C., Gao, Y., Lü, S., & Long, M. (2017) · Lab on a Chip · doi:10.1039/c6lc01374k · Cited by 241
Zhang, M., Wang, P., Luo, R., Wang, Y., Li, Z., Guo, Y., Yao, Y., Li, M., Tao, T., Chen, W., et al. (2021) · Advanced Science · doi:10.1002/advs.202002928 · Cited by 236
Reverse engineering human pathophysiology with organs-on-chips
Ingber, D. E. (2016) · Cell · doi:10.1016/j.cell.2016.02.049 · Cited by 212
Self-citationEngineering human islet organoids from iPSCs using an organ-on-chip platform
Tao, T., Wang, Y., Chen, W., Li, Z., Su, W., Guo, Y., Deng, P., & Qin, J. (2019) · Lab on a Chip · doi:10.1039/c8lc01298a · Cited by 198
A lung/liver-on-a-chip platform for acute and chronic toxicity studies
Bovard, D., Sandoz, A., Luettich, K., Frentzel, S., Iskandar, A., Marescotti, D., Trivedi, K., Guedj, E., Dutertre, Q., Peitsch, M. C., et al. (2018) · Lab on a Chip · doi:10.1039/c8lc01029c · Cited by 195
Prantil-Baun, R., Novak, R., Das, D., Somayaji, M. R., Przekwas, A., & Ingber, D. E. (2018) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010716-104748 · Cited by 176
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 175
Assessment of whole blood thrombosis in a microfluidic device lined by fixed human endothelium
Jain, A., van der Meer, A. D., Papa, A.-L., Barrile, R., Lai, A., Schlechter, B. L., Otieno, M. A., Louden, C. S., Hamilton, G. A., Michelson, A. D., et al. (2016) · Biomedical Microdevices · doi:10.1007/s10544-016-0095-6 · Cited by 148
Self-citationSimulating drug concentrations in PDMS microfluidic organ chips
Grant, J., Özkan, A., Oh, C., Mahajan, G., Prantil-Baun, R., & Ingber, D. E. (2021) · Lab on a Chip · doi:10.1039/d1lc00348h · Cited by 133
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Lee, K. K., McCauley, H. A., Broda, T. R., Kofron, M. J., Wells, J. M., & Hong, C. I. (2018) · Lab on a Chip · doi:10.1039/c8lc00910d · Cited by 129
Alimperti, S., Mirabella, T., Bajaj, V., Polacheck, W., Pirone, D. M., Duffield, J., Eyckmans, J., Assoian, R. K., & Chen, C. S. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1618333114 · Cited by 122
Progress, obstacles, and limitations in the use of stem cells in organ-on-a-chip models
Wnorowski, A., Yang, H., & Wu, J. C. (2019) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2018.06.001 · Cited by 124
Integrating Organs-on-Chips: Multiplexing, Scaling, Vascularization, and Innervation
Park, D., Lee, J., Chung, J. J., Jung, Y., & Kim, S. H. (2020) · Trends in Biotechnology · doi:10.1016/j.tibtech.2019.06.006 · Cited by 105
Intestinal organoids: A new paradigm for engineering intestinal epithelium in vitro
Rahmani, S., Breyner, N. M., Su, H.-M., Verdu, E. F., & Didar, T. F. (2019) · Biomaterials · doi:10.1016/j.biomaterials.2018.12.006 · Cited by 98
Microfluidic high-throughput 3D cell culture
Ko, J., Park, D., Lee, J., Jung, S., Baek, K., Sung, K. E., Lee, J., & Jeon, N. L. (2024) · Nature Reviews Bioengineering · doi:10.1038/s44222-024-00163-8 · Cited by 88
Ekert, J. E., Deakyne, J., Pribul-Allen, P., Terry, R., Schofield, C., Jeong, C. G., Storey, J., Mohamet, L., Francis, J., Naidoo, A., et al. (2020) · SLAS DISCOVERY · doi:10.1177/2472555220923332 · Cited by 68
Ainslie, G. R., Davis, M., Ewart, L., Lieberman, L. A., Rowlands, D. J., Thorley, A. J., Yoder, G., & Ryan, A. M. (2019) · Lab on a Chip · doi:10.1039/c9lc00492k · Cited by 65
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
A hollow fiber system for simple generation of human brain organoids
Zhu, Y., Wang, L., Yin, F., Yu, Y., Wang, Y., Liu, H., Wang, H., Sun, N., Liu, H., & Qin, J. (2017) · Integr. Biol. · doi:10.1039/c7ib00080d · Cited by 55
Sensors-integrated organ-on-a-chip for biomedical applications
Chen, H., Luo, Z., Lin, X., Zhu, Y., & Zhao, Y. (2023) · Nano Research · doi:10.1007/s12274-023-5651-9 · Cited by 47
Ayuso, J. M., Sadangi, S., Lares, M., Rehman, S., Humayun, M., Denecke, K. M., Skala, M. C., Beebe, D. J., & Setaluri, V. (2021) · Lab on a Chip · doi:10.1039/d0lc00988a · Cited by 39
Synthesizing living tissues with microfluidics
Zheng, W., & Jiang, X. (2018) · Accounts of Chemical Research · doi:10.1021/acs.accounts.8b00417 · Cited by 35
Engineering cell heterogeneity into organs-on-a-chip
Mertz, D. R., Ahmed, T., & Takayama, S. (2018) · Lab on a Chip · doi:10.1039/c8lc00413g · Cited by 33
Human stroma and epithelium co-culture in a microfluidic model of a human prostate gland
Jiang, L., Ivich, F., Tahsin, S., Tran, M., Frank, S. B., Miranti, C. K., & Zohar, Y. (2019) · Biomicrofluidics · doi:10.1063/1.5126714 · Cited by 31
Recommendations toward a human pathway-based approach to disease research
Marshall, L. J., Austin, C. P., Casey, W., Fitzpatrick, S. C., & Willett, C. (2018) · Drug Discovery Today · doi:10.1016/j.drudis.2018.05.038 · Cited by 28
Skin models of cutaneous toxicity, transdermal transport and wound repair
Vilela de Sousa, I., Ferreira, M. J. S., Bebiano, L. B., Simões, S., Matos, A. F., Pereira, R. F., & Granja, P. L. (2023) · Burns & Trauma · doi:10.1093/burnst/tkad014 · Cited by 17
Boussommier-Calleja, A. (2020) · Bioengineering Innovative Solutions for Cancer · doi:10.1016/b978-0-12-813886-1.00013-9 · Cited by 10
Baddal, B. (2022) · Cyprus Journal of Medical Sciences · doi:10.4274/cjms.2020.1426 · Cited by 6
Metadata
- Authors
- Benam, K. H., Villenave, R., Lucchesi, C., Varone, A., Hubeau, C., Lee, H.-H., Alves, S. E., Salmon, M., Ferrante, T. C., Weaver, J. C., Bahinski, A., Hamilton, G. A., & Ingber, D. E.
- Venue
- Nature Methods
- Published
- 2015-12-21
- Volume
- 13
- Issue
- 2
- Pages
- 151-157
- ISSN
- 1548-7091 (ISSN-L)
- 1548-7105
- OpenAlex
- W2256963343
- Cited by
- 816
- References
- 7
- FWCI
- 22.65
- Type
- journal article
- Language
- en
- Open access
- green
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