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Three-Dimensional Regeneration of Patient-Derived Intestinal Organoid Epithelium in a Physiodynamic Mucosal Interface-on-a-Chip.
Micromachines (Basel). 2020 Jul 07; 11(7)M

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.

Authors+Show Affiliations

Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX 78712, USA.Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX 78712, USA.Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX 78712, USA.Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX 78712, USA.Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX 78712, USA.Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX 78712, USA.Department of Oncology, Dell Medical School, The University of Texas at Austin, Austin, TX 78712, USA.Department of Oncology, Dell Medical School, The University of Texas at Austin, Austin, TX 78712, USA. Department of Surgery and Perioperative Care, Dell Medical School, The University of Texas at Austin, Austin, TX 78712, USA.Severance Fecal Microbiota Transplantation Center, Severance Hospital, Department of Pediatrics, Yonsei University College of Medicine, Seoul 03722, Korea.Severance Fecal Microbiota Transplantation Center, Severance Hospital, Department of Pediatrics, Yonsei University College of Medicine, Seoul 03722, Korea.Severance Fecal Microbiota Transplantation Center, Severance Hospital, Department of Pediatrics, Yonsei University College of Medicine, Seoul 03722, Korea.Department of Computer Art, College of Art and Technology, Chung-Ang University, Seoul 06974, Korea.Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX 78712, USA. Department of Oncology, Dell Medical School, The University of Texas at Austin, Austin, TX 78712, USA. Department of Medical Engineering, College of Medicine, Yonsei University, Seoul 03722, Korea.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32645991

Citation

Shin, Yong Cheol, et al. "Three-Dimensional Regeneration of Patient-Derived Intestinal Organoid Epithelium in a Physiodynamic Mucosal Interface-on-a-Chip." Micromachines, vol. 11, no. 7, 2020.
Shin YC, Shin W, Koh D, et al. Three-Dimensional Regeneration of Patient-Derived Intestinal Organoid Epithelium in a Physiodynamic Mucosal Interface-on-a-Chip. Micromachines (Basel). 2020;11(7).
Shin, Y. C., Shin, W., Koh, D., Wu, A., Ambrosini, Y. M., Min, S., Eckhardt, S. G., Fleming, R. Y. D., Kim, S., Park, S., Koh, H., Yoo, T. K., & Kim, H. J. (2020). Three-Dimensional Regeneration of Patient-Derived Intestinal Organoid Epithelium in a Physiodynamic Mucosal Interface-on-a-Chip. Micromachines, 11(7). https://doi.org/10.3390/mi11070663
Shin YC, et al. Three-Dimensional Regeneration of Patient-Derived Intestinal Organoid Epithelium in a Physiodynamic Mucosal Interface-on-a-Chip. Micromachines (Basel). 2020 Jul 7;11(7) PubMed PMID: 32645991.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Three-Dimensional Regeneration of Patient-Derived Intestinal Organoid Epithelium in a Physiodynamic Mucosal Interface-on-a-Chip. AU - Shin,Yong Cheol, AU - Shin,Woojung, AU - Koh,Domin, AU - Wu,Alexander, AU - Ambrosini,Yoko M, AU - Min,Soyoun, AU - Eckhardt,S Gail, AU - Fleming,R Y Declan, AU - Kim,Seung, AU - Park,Sowon, AU - Koh,Hong, AU - Yoo,Tae Kyung, AU - Kim,Hyun Jung, Y1 - 2020/07/07/ PY - 2020/05/01/received PY - 2020/07/03/revised PY - 2020/07/05/accepted PY - 2020/7/11/entrez KW - co-culture KW - disease modeling KW - gut-on-a-chip KW - microbiome KW - mucosal interface KW - multiaxial deformation KW - organoid KW - physiodynamic JF - Micromachines JO - Micromachines (Basel) VL - 11 IS - 7 N2 - 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. SN - 2072-666X UR - https://www.unboundmedicine.com/medline/citation/32645991/Three-Dimensional_Regeneration_of_Patient-Derived_Intestinal_Organoid_Epithelium_in_a_Physiodynamic_Mucosal_Interface-on-a-Chip DB - PRIME DP - Unbound Medicine ER -
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