Small airway-on-a-chip enables analysis of human lung inflammation and drug responses in vitro
The small airway-on-a-chip allows the recapitulation of human lung pathophysiology in vitro and analysis of responses to drugs. Here we describe the development of a human lung 'small airway-on-a-chip' containing a differentiated, mucociliary bronchiolar epithelium and an underlying microv...
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Veröffentlicht in: | Nature methods 2016-02, Vol.13 (2), p.151-157 |
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creator | Benam, Kambez H Villenave, Remi Lucchesi, Carolina Varone, Antonio Hubeau, Cedric Lee, Hyun-Hee Alves, Stephen E Salmon, Michael Ferrante, Thomas C Weaver, James C Bahinski, Anthony Hamilton, Geraldine A Ingber, Donald E |
description | The small airway-on-a-chip allows the recapitulation of human lung pathophysiology
in vitro
and analysis of responses to drugs.
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. |
doi_str_mv | 10.1038/nmeth.3697 |
format | Article |
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in vitro
and analysis of responses to drugs.
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.</description><identifier>ISSN: 1548-7091</identifier><identifier>EISSN: 1548-7105</identifier><identifier>DOI: 10.1038/nmeth.3697</identifier><identifier>PMID: 26689262</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>13 ; 13/1 ; 13/106 ; 13/107 ; 13/21 ; 13/31 ; 13/51 ; 13/62 ; 14 ; 14/19 ; 14/28 ; 14/34 ; 14/63 ; 631/1647/277 ; 631/250/127 ; 631/443/1784 ; 692/308/575 ; Analysis ; Asthma ; Bacterial diseases ; Bioinformatics ; Biological Microscopy ; Biological Techniques ; Biomedical Engineering/Biotechnology ; Care and treatment ; Chronic obstructive pulmonary disease ; Drug metabolism ; Drugs ; Epithelium - drug effects ; Humans ; Immune response ; Inflammation ; Inflammation - metabolism ; Inflammation - pathology ; Interleukin-13 - pharmacology ; Lab-On-A-Chip Devices ; Life Sciences ; Lung Diseases - drug therapy ; Lung Diseases - metabolism ; Lungs ; Observations ; Pathology ; Physiology ; Proteomics ; Regulation ; Synergistic effect ; Tissue Culture Techniques</subject><ispartof>Nature methods, 2016-02, Vol.13 (2), p.151-157</ispartof><rights>Springer Nature America, Inc. 2015</rights><rights>COPYRIGHT 2016 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Feb 2016</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c557t-5943cd869b4d1c121e826c772d34a4ae0b6044800710ca4157afea3cd1bd38173</citedby><cites>FETCH-LOGICAL-c557t-5943cd869b4d1c121e826c772d34a4ae0b6044800710ca4157afea3cd1bd38173</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/nmeth.3697$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/nmeth.3697$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27922,27923,41486,42555,51317</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26689262$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Benam, Kambez H</creatorcontrib><creatorcontrib>Villenave, Remi</creatorcontrib><creatorcontrib>Lucchesi, Carolina</creatorcontrib><creatorcontrib>Varone, Antonio</creatorcontrib><creatorcontrib>Hubeau, Cedric</creatorcontrib><creatorcontrib>Lee, Hyun-Hee</creatorcontrib><creatorcontrib>Alves, Stephen E</creatorcontrib><creatorcontrib>Salmon, Michael</creatorcontrib><creatorcontrib>Ferrante, Thomas C</creatorcontrib><creatorcontrib>Weaver, James C</creatorcontrib><creatorcontrib>Bahinski, Anthony</creatorcontrib><creatorcontrib>Hamilton, Geraldine A</creatorcontrib><creatorcontrib>Ingber, Donald E</creatorcontrib><title>Small airway-on-a-chip enables analysis of human lung inflammation and drug responses in vitro</title><title>Nature methods</title><addtitle>Nat Methods</addtitle><addtitle>Nat Methods</addtitle><description>The small airway-on-a-chip allows the recapitulation of human lung pathophysiology
in vitro
and analysis of responses to drugs.
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.</description><subject>13</subject><subject>13/1</subject><subject>13/106</subject><subject>13/107</subject><subject>13/21</subject><subject>13/31</subject><subject>13/51</subject><subject>13/62</subject><subject>14</subject><subject>14/19</subject><subject>14/28</subject><subject>14/34</subject><subject>14/63</subject><subject>631/1647/277</subject><subject>631/250/127</subject><subject>631/443/1784</subject><subject>692/308/575</subject><subject>Analysis</subject><subject>Asthma</subject><subject>Bacterial diseases</subject><subject>Bioinformatics</subject><subject>Biological Microscopy</subject><subject>Biological 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E</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Small airway-on-a-chip enables analysis of human lung inflammation and drug responses in vitro</atitle><jtitle>Nature methods</jtitle><stitle>Nat Methods</stitle><addtitle>Nat Methods</addtitle><date>2016-02-01</date><risdate>2016</risdate><volume>13</volume><issue>2</issue><spage>151</spage><epage>157</epage><pages>151-157</pages><issn>1548-7091</issn><eissn>1548-7105</eissn><abstract>The small airway-on-a-chip allows the recapitulation of human lung pathophysiology
in vitro
and analysis of responses to drugs.
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.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>26689262</pmid><doi>10.1038/nmeth.3697</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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title | Small airway-on-a-chip enables analysis of human lung inflammation and drug responses in vitro |
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