Journal article
Derivation of adult canine intestinal organoids for translational research in gastroenterology
BMC biology, Vol.17(1), pp.33-33
04/11/2019
DOI: 10.1186/s12915-019-0652-6
PMCID: PMC6460554
PMID: 30975131
Abstract
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.
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.
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.
Details
- Title: Subtitle
- Derivation of adult canine intestinal organoids for translational research in gastroenterology
- Creators
- Lawrance Chandra - Iowa State UniversityDana C Borcherding - Iowa State UniversityDawn Kingsbury - Iowa State UniversityTodd Atherly - Iowa State UniversityYoko M Ambrosini - Iowa State UniversityAgnes Bourgois-Mochel - Iowa State UniversityWang Yuan - Iowa State UniversityMichael Kimber - Iowa State UniversityYijun Qi - Iowa State UniversityQun Wang - Iowa State UniversityMichael Wannemuehler - Iowa State UniversityN Matthew Ellinwood - Iowa State UniversityElizabeth Snella - Iowa State UniversityMartin Martin - University of California, Los AngelesMelissa Skala - University of Wisconsin–MadisonDavid Meyerholz - University of IowaMary Estes - Baylor College of MedicineMartin E Fernandez-Zapico - Schulze Center for Novel Therapeutics, Division of Oncology Research, Mayo Clinic, Rochester, MN, USAAlbert E Jergens - Iowa State UniversityJonathan P Mochel - Iowa State UniversityKarin Allenspach - Iowa State University
- Resource Type
- Journal article
- Publication Details
- BMC biology, Vol.17(1), pp.33-33
- DOI
- 10.1186/s12915-019-0652-6
- PMID
- 30975131
- PMCID
- PMC6460554
- NLM abbreviation
- BMC Biol
- ISSN
- 1741-7007
- eISSN
- 1741-7007
- Grant note
- P30 DK054759 / NIDDK NIH HHS U01 DK085535 / NIDDK NIH HHS R01 NS085381 / NINDS NIH HHS
- Language
- English
- Date published
- 04/11/2019
- Academic Unit
- Microbiology and Immunology; Pathology
- Record Identifier
- 9984186646802771
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