Three-dimensional regeneration of patient-derived intestinal organoid epithelium in a physiodynamic mucosal interface-on-a-chip
- Authors
- Shin, Y.C.; Shin, W.; Koh, D.; Wu, A.; Ambrosini, Y.M.; Min, S.; Gail Eckhardt, S.; Declan Fleming, R.Y.; Kim, S.; Park, S.; Koh, H.; Yoo, T.K.; Kim, H.J.
- Issue Date
- Jul-2020
- Publisher
- MDPI AG
- Keywords
- Co-culture; Disease modeling; Gut-on-a-chip; Microbiome; Mucosal interface; Multiaxial deformation; Organoid; Physiodynamic
- Citation
- Micromachines, v.11, no.7
- Journal Title
- Micromachines
- Volume
- 11
- Number
- 7
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/63375
- DOI
- 10.3390/mi11070663
- ISSN
- 2072-666X
2072-666X
- Abstract
- 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. © 2020 by the authors.
- Files in This Item
- There are no files associated with this item.
- Appears in
Collections - ETC > 1. Journal Articles
![qrcode](https://api.qrserver.com/v1/create-qr-code/?size=55x55&data=https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/63375)
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.