期刊
MICROMACHINES
卷 11, 期 7, 页码 -出版社
MDPI
DOI: 10.3390/mi11070663
关键词
gut-on-a-chip; organoid; mucosal interface; physiodynamic; multiaxial deformation; microbiome; co-culture; disease modeling
类别
资金
- National Cancer Institute of the National Institutes of Health (NIH/NCI) [F99CA245801]
- Asan Foundation Biomedical Science Scholarship
- Burroughs Wellcome Fund Collaborative Research Travel Grant [BWF 1019990.01]
- American College of Veterinary Internal Medicine Advance Research Fellowships [771066]
- Bio & Medical Technology Development Program of the National Research Foundation - Ministry of Science and ICT [2018M3A9H3025030]
- Technology Impact Award of the Cancer Research Institute [UTA18-000889]
- NIH/NCI [R21CA236690]
- Leona M. & Harry B. Helmsley Charitable Trust [1912-03604]
- Cancer Prevention and Research Institute of Texas (CPRIT) Scholar Award [RR160093]
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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