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

 Yong Cheol Shin  ;  Woojung Shin  ;  Domin Koh  ;  Alexander Wu  ;  Yoko M Ambrosini  ;  Soyoun Min  ;  S Gail Eckhardt  ;  R Y Declan Fleming  ;  Seung Kim  ;  Sowon Park  ;  Hong Koh  ;  Tae Kyung Yoo  ;  Hyun Jung Kim 
 MICROMACHINES, Vol.11(7) : 663, 2020-07 
Journal Title
Issue Date
co-culture ; disease modeling ; gut-on-a-chip ; microbiome ; mucosal interface ; multiaxial deformation ; organoid ; physiodynamic
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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1. College of Medicine (의과대학) > Dept. of Pediatrics (소아과학교실) > 1. Journal Papers
Yonsei Authors
Koh, Hong(고홍) ORCID logo https://orcid.org/0000-0002-3660-7483
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