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Three-Dimensional Regeneration of Patient-Derived Intestinal Organoid Epithelium in a Physiodynamic Mucosal Interface-on-a-Chip

The regeneration of the mucosal interface of the human intestine is critical in the host–gut microbiome crosstalk associated with gastrointestinal diseases. The biopsy-derived intestinal organoids provide genetic information of patients with physiological cytodifferentiation. However, the enclosed l...

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Autores principales: Shin, Yong Cheol, Shin, Woojung, Koh, Domin, Wu, Alexander, Ambrosini, Yoko M., Min, Soyoun, Eckhardt, S. Gail, Fleming, R. Y. Declan, Kim, Seung, Park, Sowon, Koh, Hong, Yoo, Tae Kyung, Kim, Hyun Jung
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7408321/
https://www.ncbi.nlm.nih.gov/pubmed/32645991
http://dx.doi.org/10.3390/mi11070663
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author Shin, Yong Cheol
Shin, Woojung
Koh, Domin
Wu, Alexander
Ambrosini, Yoko M.
Min, Soyoun
Eckhardt, S. Gail
Fleming, R. Y. Declan
Kim, Seung
Park, Sowon
Koh, Hong
Yoo, Tae Kyung
Kim, Hyun Jung
author_facet Shin, Yong Cheol
Shin, Woojung
Koh, Domin
Wu, Alexander
Ambrosini, Yoko M.
Min, Soyoun
Eckhardt, S. Gail
Fleming, R. Y. Declan
Kim, Seung
Park, Sowon
Koh, Hong
Yoo, Tae Kyung
Kim, Hyun Jung
author_sort Shin, Yong Cheol
collection PubMed
description The regeneration of the mucosal interface of the human intestine is critical in the host–gut microbiome crosstalk associated with gastrointestinal diseases. The biopsy-derived intestinal organoids provide genetic information of patients with physiological cytodifferentiation. However, the enclosed lumen and static culture condition substantially limit the utility of patient-derived organoids for microbiome-associated disease modeling. Here, we report a patient-specific three-dimensional (3D) physiodynamic mucosal interface-on-a-chip (PMI Chip) that provides a microphysiological intestinal milieu under defined biomechanics. The real-time imaging and computational simulation of the PMI Chip verified the recapitulation of non-linear luminal and microvascular flow that simulates the hydrodynamics in a living human gut. The multiaxial deformations in a convoluted microchannel not only induced dynamic cell strains but also enhanced particle mixing in the lumen microchannel. Under this physiodynamic condition, an organoid-derived epithelium obtained from the patients diagnosed with Crohn’s disease, ulcerative colitis, or colorectal cancer independently formed 3D epithelial layers with disease-specific differentiations. Moreover, co-culture with the human fecal microbiome in an anoxic–oxic interface resulted in the formation of stochastic microcolonies without a loss of epithelial barrier function. We envision that the patient-specific PMI Chip that conveys genetic, epigenetic, and environmental factors of individual patients will potentially demonstrate the pathophysiological dynamics and complex host–microbiome crosstalk to target a patient-specific disease modeling.
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spelling pubmed-74083212020-08-13 Three-Dimensional Regeneration of Patient-Derived Intestinal Organoid Epithelium in a Physiodynamic Mucosal Interface-on-a-Chip Shin, Yong Cheol Shin, Woojung Koh, Domin Wu, Alexander Ambrosini, Yoko M. Min, Soyoun Eckhardt, S. Gail Fleming, R. Y. Declan Kim, Seung Park, Sowon Koh, Hong Yoo, Tae Kyung Kim, Hyun Jung Micromachines (Basel) Article The regeneration of the mucosal interface of the human intestine is critical in the host–gut microbiome crosstalk associated with gastrointestinal diseases. The biopsy-derived intestinal organoids provide genetic information of patients with physiological cytodifferentiation. However, the enclosed lumen and static culture condition substantially limit the utility of patient-derived organoids for microbiome-associated disease modeling. Here, we report a patient-specific three-dimensional (3D) physiodynamic mucosal interface-on-a-chip (PMI Chip) that provides a microphysiological intestinal milieu under defined biomechanics. The real-time imaging and computational simulation of the PMI Chip verified the recapitulation of non-linear luminal and microvascular flow that simulates the hydrodynamics in a living human gut. The multiaxial deformations in a convoluted microchannel not only induced dynamic cell strains but also enhanced particle mixing in the lumen microchannel. Under this physiodynamic condition, an organoid-derived epithelium obtained from the patients diagnosed with Crohn’s disease, ulcerative colitis, or colorectal cancer independently formed 3D epithelial layers with disease-specific differentiations. Moreover, co-culture with the human fecal microbiome in an anoxic–oxic interface resulted in the formation of stochastic microcolonies without a loss of epithelial barrier function. We envision that the patient-specific PMI Chip that conveys genetic, epigenetic, and environmental factors of individual patients will potentially demonstrate the pathophysiological dynamics and complex host–microbiome crosstalk to target a patient-specific disease modeling. MDPI 2020-07-07 /pmc/articles/PMC7408321/ /pubmed/32645991 http://dx.doi.org/10.3390/mi11070663 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Shin, Yong Cheol
Shin, Woojung
Koh, Domin
Wu, Alexander
Ambrosini, Yoko M.
Min, Soyoun
Eckhardt, S. Gail
Fleming, R. Y. Declan
Kim, Seung
Park, Sowon
Koh, Hong
Yoo, Tae Kyung
Kim, Hyun Jung
Three-Dimensional Regeneration of Patient-Derived Intestinal Organoid Epithelium in a Physiodynamic Mucosal Interface-on-a-Chip
title Three-Dimensional Regeneration of Patient-Derived Intestinal Organoid Epithelium in a Physiodynamic Mucosal Interface-on-a-Chip
title_full Three-Dimensional Regeneration of Patient-Derived Intestinal Organoid Epithelium in a Physiodynamic Mucosal Interface-on-a-Chip
title_fullStr Three-Dimensional Regeneration of Patient-Derived Intestinal Organoid Epithelium in a Physiodynamic Mucosal Interface-on-a-Chip
title_full_unstemmed Three-Dimensional Regeneration of Patient-Derived Intestinal Organoid Epithelium in a Physiodynamic Mucosal Interface-on-a-Chip
title_short Three-Dimensional Regeneration of Patient-Derived Intestinal Organoid Epithelium in a Physiodynamic Mucosal Interface-on-a-Chip
title_sort three-dimensional regeneration of patient-derived intestinal organoid epithelium in a physiodynamic mucosal interface-on-a-chip
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7408321/
https://www.ncbi.nlm.nih.gov/pubmed/32645991
http://dx.doi.org/10.3390/mi11070663
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