Title
Derivation of adult canine intestinal organoids for translational research in gastroenterology
Campus Units
Biomedical Sciences, Veterinary Clinical Sciences, Chemical and Biological Engineering, Veterinary Microbiology and Preventive Medicine, Animal Science
Document Type
Article
Publication Version
Published Version
Publication Date
4-11-2019
Journal or Book Title
BMC Biology
Volume
17
First Page
33
DOI
10.1186/s12915-019-0652-6
Abstract
Background: Large animal models, such as the dog, are increasingly being used for studying diseases including gastrointestinal (GI) disorders. Dogs share similar environmental, genomic, anatomical, and intestinal physiologic features with humans. To bridge the gap between commonly used animal models, such as rodents, and humans, and expand the translational potential of the dog model, we developed a three-dimensional (3D) canine GI organoid (enteroid and colonoid) system. Organoids have recently gained interest in translational research as this model system better recapitulates the physiological and molecular features of the tissue environment in comparison with two-dimensional cultures.
Results: Organoids were derived from tissue of more than 40 healthy dogs and dogs with GI conditions, including inflammatory bowel disease (IBD) and intestinal carcinomas. Adult intestinal stem cells (ISC) were isolated from whole jejunal tissue as well as endoscopically obtained duodenal, ileal, and colonic biopsy samples using an optimized culture protocol. Intestinal organoids were comprehensively characterized using histology, immunohistochemistry, RNA in situ hybridization, and transmission electron microscopy, to determine the extent to which they recapitulated the in vivo tissue characteristics. Physiological relevance of the enteroid system was defined using functional assays such as optical metabolic imaging (OMI), the cystic fibrosis transmembrane conductance regulator (CFTR) function assay, and Exosome-Like Vesicles (EV) uptake assay, as a basis for wider applications of this technology in basic, preclinical and translational GI research. We have furthermore created a collection of cryopreserved organoids to facilitate future research.
Conclusions: We establish the canine GI organoid systems as a model to study naturally occurring intestinal diseases in dogs and humans, and that can be used for toxicology studies, for analysis of host-pathogen interactions, and for other translational applications.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Copyright Owner
The Author(s)
Copyright Date
2019
Language
en
File Format
application/pdf
Recommended Citation
Chandra, Lawrance; Borcherding, Dana C.; Kingsbury, Dawn; Atherly, Todd; Ambrosini, Yoko M.; Bourgois-Mochel, Agnes; Yuan, Wang; Kimber, Michael J.; Qi, Yijun; Wang, Qun; Wannemeuhler, Michael; Ellinwood, N. Matthew; Snella, Elizabeth; Martin, Martin; Skala, Melissa; Meyerholz, David; Estes, Mary; Fernandez-Zapico, Martin E.; Jergens, Albert E.; Mochel, Jonathan P.; and Allenspach, Karin, "Derivation of adult canine intestinal organoids for translational research in gastroenterology" (2019). Biomedical Sciences Publications. 75.
https://lib.dr.iastate.edu/bms_pubs/75
Included in
Analytical, Diagnostic and Therapeutic Techniques and Equipment Commons, Digestive System Commons, Gastroenterology Commons, Small or Companion Animal Medicine Commons
Comments
This article is published as Chandra, Lawrance, Dana C. Borcherding, Dawn Kingsbury, Todd Atherly, Yoko M. Ambrosini, Agnes Bourgois-Mochel, Wang Yuan, Michael Kimber, Yijun Qi, Qun Wang, Michael Wannemuehler, N. Matthew Ellinwood, Elizabeth Snella, Martin Martin, Melissa Skala, David Meyerholz, Mary Estes, Martin E. Fernandez-Zapico, Albert E. Jergens, Jonathan P. Mochel, and Karin Allenspach. "Derivation of adult canine intestinal organoids for translational research in gastroenterology." BMC Biology 17 (2019): 33. DOI: 10.1186/s12915-019-0652-6. Posted with permission.