A platform to reproducibly evaluate human colon permeability and damage
Abstract The intestinal epithelium comprises diverse cell types and executes many specialized functions as the primary interface between luminal contents and internal organs. A key function provided by the epithelium is maintenance of a barrier that protects the individual from pathogens, irritating...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-06-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-36020-8 |
| _version_ | 1797811469842120704 |
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| author | Elizabeth E. Marr Thomas J. Mulhern Michaela Welch Philip Keegan Celia Caballero-Franco Bryce G. Johnson Marion Kasaian Hesham Azizgolshani Timothy Petrie Joseph Charest Elizabeth Wiellette |
| author_facet | Elizabeth E. Marr Thomas J. Mulhern Michaela Welch Philip Keegan Celia Caballero-Franco Bryce G. Johnson Marion Kasaian Hesham Azizgolshani Timothy Petrie Joseph Charest Elizabeth Wiellette |
| author_sort | Elizabeth E. Marr |
| collection | DOAJ |
| description | Abstract The intestinal epithelium comprises diverse cell types and executes many specialized functions as the primary interface between luminal contents and internal organs. A key function provided by the epithelium is maintenance of a barrier that protects the individual from pathogens, irritating luminal contents, and the microbiota. Disruption of this barrier can lead to inflammatory disease within the intestinal mucosa, and, in more severe cases, to sepsis. Animal models to study intestinal permeability are costly and not entirely predictive of human biology. Here we present a model of human colon barrier function that integrates primary human colon stem cells into Draper’s PREDICT96 microfluidic organ-on-chip platform to yield a high-throughput system appropriate to predict damage and healing of the human colon epithelial barrier. We have demonstrated pharmacologically induced barrier damage measured by both a high throughput molecular permeability assay and transepithelial resistance. Using these assays, we developed an Inflammatory Bowel Disease-relevant model through cytokine induced damage that can support studies of disease mechanisms and putative therapeutics. |
| first_indexed | 2024-03-13T07:24:00Z |
| format | Article |
| id | doaj.art-1833cfd34b4e4f38827ff34d22a11b00 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-13T07:24:00Z |
| publishDate | 2023-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-1833cfd34b4e4f38827ff34d22a11b002023-06-04T11:27:50ZengNature PortfolioScientific Reports2045-23222023-06-0113111510.1038/s41598-023-36020-8A platform to reproducibly evaluate human colon permeability and damageElizabeth E. Marr0Thomas J. Mulhern1Michaela Welch2Philip Keegan3Celia Caballero-Franco4Bryce G. Johnson5Marion Kasaian6Hesham Azizgolshani7Timothy Petrie8Joseph Charest9Elizabeth Wiellette10DraperDraperDraperDraperPfizer Inflammation and ImmunologyPfizer Inflammation and ImmunologyPfizer Inflammation and ImmunologyDraperDraperDraperDraperAbstract The intestinal epithelium comprises diverse cell types and executes many specialized functions as the primary interface between luminal contents and internal organs. A key function provided by the epithelium is maintenance of a barrier that protects the individual from pathogens, irritating luminal contents, and the microbiota. Disruption of this barrier can lead to inflammatory disease within the intestinal mucosa, and, in more severe cases, to sepsis. Animal models to study intestinal permeability are costly and not entirely predictive of human biology. Here we present a model of human colon barrier function that integrates primary human colon stem cells into Draper’s PREDICT96 microfluidic organ-on-chip platform to yield a high-throughput system appropriate to predict damage and healing of the human colon epithelial barrier. We have demonstrated pharmacologically induced barrier damage measured by both a high throughput molecular permeability assay and transepithelial resistance. Using these assays, we developed an Inflammatory Bowel Disease-relevant model through cytokine induced damage that can support studies of disease mechanisms and putative therapeutics.https://doi.org/10.1038/s41598-023-36020-8 |
| spellingShingle | Elizabeth E. Marr Thomas J. Mulhern Michaela Welch Philip Keegan Celia Caballero-Franco Bryce G. Johnson Marion Kasaian Hesham Azizgolshani Timothy Petrie Joseph Charest Elizabeth Wiellette A platform to reproducibly evaluate human colon permeability and damage Scientific Reports |
| title | A platform to reproducibly evaluate human colon permeability and damage |
| title_full | A platform to reproducibly evaluate human colon permeability and damage |
| title_fullStr | A platform to reproducibly evaluate human colon permeability and damage |
| title_full_unstemmed | A platform to reproducibly evaluate human colon permeability and damage |
| title_short | A platform to reproducibly evaluate human colon permeability and damage |
| title_sort | platform to reproducibly evaluate human colon permeability and damage |
| url | https://doi.org/10.1038/s41598-023-36020-8 |
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