A Novel Microphysiological Colon Platform to Decipher Mechanisms Driving Human Intestinal PermeabilitySummary
Background & Aims: The limited availability of organoid systems that mimic the molecular signatures and architecture of human intestinal epithelium has been an impediment to allowing them to be harnessed for the development of therapeutics as well as physiological insights. We developed a mi...
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Elsevier
2021
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oai:doaj.org-article:8581303f9bfe4c679f3e7c038c1061c82021-11-12T04:38:56ZA Novel Microphysiological Colon Platform to Decipher Mechanisms Driving Human Intestinal PermeabilitySummary2352-345X10.1016/j.jcmgh.2021.07.004https://doaj.org/article/8581303f9bfe4c679f3e7c038c1061c82021-01-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2352345X21001454https://doaj.org/toc/2352-345XBackground & Aims: The limited availability of organoid systems that mimic the molecular signatures and architecture of human intestinal epithelium has been an impediment to allowing them to be harnessed for the development of therapeutics as well as physiological insights. We developed a microphysiological Organ-on-Chip (Emulate, Inc, Boston, MA) platform designed to mimic properties of human intestinal epithelium leading to insights into barrier integrity. Methods: We combined the human biopsy-derived leucine-rich repeat-containing G-protein–coupled receptor 5–positive organoids and Organ-on-Chip technologies to establish a micro-engineered human Colon Intestine-Chip (Emulate, Inc, Boston, MA). We characterized the proximity of the model to human tissue and organoids maintained in suspension by RNA sequencing analysis, and their differentiation to intestinal epithelial cells on the Colon Intestine-Chip under variable conditions. Furthermore, organoids from different donors were evaluated to understand variability in the system. Our system was applied to understanding the epithelial barrier and characterizing mechanisms driving the cytokine-induced barrier disruption. Results: Our data highlight the importance of the endothelium and the in vivo tissue-relevant dynamic microenvironment in the Colon Intestine-Chip in the establishment of a tight monolayer of differentiated, polarized, organoid-derived intestinal epithelial cells. We confirmed the effect of interferon-γ on the colonic barrier and identified reorganization of apical junctional complexes, and induction of apoptosis in the intestinal epithelial cells as mediating mechanisms. We show that in the human Colon Intestine-Chip exposure to interleukin 22 induces disruption of the barrier, unlike its described protective role in experimental colitis in mice. Conclusions: We developed a human Colon Intestine-Chip platform and showed its value in the characterization of the mechanism of action of interleukin 22 in the human epithelial barrier. This system can be used to elucidate, in a time- and challenge-dependent manner, the mechanism driving the development of leaky gut in human beings and to identify associated biomarkers.Athanasia ApostolouRohit A. PanchakshariAntara BanerjeeDimitris V. ManatakisMaria D. ParaskevopoulouRaymond LucGaleb Abu-AliAlexandra DimitriouCarolina LucchesiGauri KulkarniTengku Ibrahim MaulanaMagdalena KasendraJordan S. KernsBertram BleckLorna EwartElias S. ManolakosGeraldine A. HamiltonCosmas GiallourakisKatia KaralisElsevierarticleOrganoidsOrgan-on-ChipLeaky GutInterleukin 22Diseases of the digestive system. GastroenterologyRC799-869ENCellular and Molecular Gastroenterology and Hepatology, Vol 12, Iss 5, Pp 1719-1741 (2021) |
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Organoids Organ-on-Chip Leaky Gut Interleukin 22 Diseases of the digestive system. Gastroenterology RC799-869 |
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Organoids Organ-on-Chip Leaky Gut Interleukin 22 Diseases of the digestive system. Gastroenterology RC799-869 Athanasia Apostolou Rohit A. Panchakshari Antara Banerjee Dimitris V. Manatakis Maria D. Paraskevopoulou Raymond Luc Galeb Abu-Ali Alexandra Dimitriou Carolina Lucchesi Gauri Kulkarni Tengku Ibrahim Maulana Magdalena Kasendra Jordan S. Kerns Bertram Bleck Lorna Ewart Elias S. Manolakos Geraldine A. Hamilton Cosmas Giallourakis Katia Karalis A Novel Microphysiological Colon Platform to Decipher Mechanisms Driving Human Intestinal PermeabilitySummary |
| description |
Background & Aims: The limited availability of organoid systems that mimic the molecular signatures and architecture of human intestinal epithelium has been an impediment to allowing them to be harnessed for the development of therapeutics as well as physiological insights. We developed a microphysiological Organ-on-Chip (Emulate, Inc, Boston, MA) platform designed to mimic properties of human intestinal epithelium leading to insights into barrier integrity. Methods: We combined the human biopsy-derived leucine-rich repeat-containing G-protein–coupled receptor 5–positive organoids and Organ-on-Chip technologies to establish a micro-engineered human Colon Intestine-Chip (Emulate, Inc, Boston, MA). We characterized the proximity of the model to human tissue and organoids maintained in suspension by RNA sequencing analysis, and their differentiation to intestinal epithelial cells on the Colon Intestine-Chip under variable conditions. Furthermore, organoids from different donors were evaluated to understand variability in the system. Our system was applied to understanding the epithelial barrier and characterizing mechanisms driving the cytokine-induced barrier disruption. Results: Our data highlight the importance of the endothelium and the in vivo tissue-relevant dynamic microenvironment in the Colon Intestine-Chip in the establishment of a tight monolayer of differentiated, polarized, organoid-derived intestinal epithelial cells. We confirmed the effect of interferon-γ on the colonic barrier and identified reorganization of apical junctional complexes, and induction of apoptosis in the intestinal epithelial cells as mediating mechanisms. We show that in the human Colon Intestine-Chip exposure to interleukin 22 induces disruption of the barrier, unlike its described protective role in experimental colitis in mice. Conclusions: We developed a human Colon Intestine-Chip platform and showed its value in the characterization of the mechanism of action of interleukin 22 in the human epithelial barrier. This system can be used to elucidate, in a time- and challenge-dependent manner, the mechanism driving the development of leaky gut in human beings and to identify associated biomarkers. |
| format |
article |
| author |
Athanasia Apostolou Rohit A. Panchakshari Antara Banerjee Dimitris V. Manatakis Maria D. Paraskevopoulou Raymond Luc Galeb Abu-Ali Alexandra Dimitriou Carolina Lucchesi Gauri Kulkarni Tengku Ibrahim Maulana Magdalena Kasendra Jordan S. Kerns Bertram Bleck Lorna Ewart Elias S. Manolakos Geraldine A. Hamilton Cosmas Giallourakis Katia Karalis |
| author_facet |
Athanasia Apostolou Rohit A. Panchakshari Antara Banerjee Dimitris V. Manatakis Maria D. Paraskevopoulou Raymond Luc Galeb Abu-Ali Alexandra Dimitriou Carolina Lucchesi Gauri Kulkarni Tengku Ibrahim Maulana Magdalena Kasendra Jordan S. Kerns Bertram Bleck Lorna Ewart Elias S. Manolakos Geraldine A. Hamilton Cosmas Giallourakis Katia Karalis |
| author_sort |
Athanasia Apostolou |
| title |
A Novel Microphysiological Colon Platform to Decipher Mechanisms Driving Human Intestinal PermeabilitySummary |
| title_short |
A Novel Microphysiological Colon Platform to Decipher Mechanisms Driving Human Intestinal PermeabilitySummary |
| title_full |
A Novel Microphysiological Colon Platform to Decipher Mechanisms Driving Human Intestinal PermeabilitySummary |
| title_fullStr |
A Novel Microphysiological Colon Platform to Decipher Mechanisms Driving Human Intestinal PermeabilitySummary |
| title_full_unstemmed |
A Novel Microphysiological Colon Platform to Decipher Mechanisms Driving Human Intestinal PermeabilitySummary |
| title_sort |
novel microphysiological colon platform to decipher mechanisms driving human intestinal permeabilitysummary |
| publisher |
Elsevier |
| publishDate |
2021 |
| url |
https://doaj.org/article/8581303f9bfe4c679f3e7c038c1061c8 |
| work_keys_str_mv |
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