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
Affiliations
Yong Cheol Shin
Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX 78712, USA
Woojung Shin
Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX 78712, USA
Domin Koh
Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX 78712, USA
Alexander Wu
Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX 78712, USA
Yoko M. Ambrosini
Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX 78712, USA
Soyoun Min
Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX 78712, USA
S. Gail Eckhardt
Department of Oncology, Dell Medical School, The University of Texas at Austin, Austin, TX 78712, USA
R. Y. Declan Fleming
Department of Oncology, Dell Medical School, The University of Texas at Austin, Austin, TX 78712, USA
Seung Kim
Severance Fecal Microbiota Transplantation Center, Severance Hospital, Department of Pediatrics, Yonsei University College of Medicine, Seoul 03722, Korea
Sowon Park
Severance Fecal Microbiota Transplantation Center, Severance Hospital, Department of Pediatrics, Yonsei University College of Medicine, Seoul 03722, Korea
Hong Koh
Severance Fecal Microbiota Transplantation Center, Severance Hospital, Department of Pediatrics, Yonsei University College of Medicine, Seoul 03722, Korea
Tae Kyung Yoo
Department of Computer Art, College of Art and Technology, Chung-Ang University, Seoul 06974, Korea
Hyun Jung Kim
Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX 78712, USA
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.
