Derivation of adult canine intestinal organoids for translational research in gastroenterology

dc.contributor.author Kimber, Michael
dc.contributor.author Chandra, Lawrance
dc.contributor.author Borcherding, Dana
dc.contributor.author Kingsbury, Dawn
dc.contributor.author Atherly, Todd
dc.contributor.author Ambrosini, Yoko
dc.contributor.author Mochel, Jonathan
dc.contributor.author Bourgois-Mochel, Agnes
dc.contributor.author Yuan, Wang
dc.contributor.author Kimber, Michael
dc.contributor.author Qi, Yijun
dc.contributor.author Wang, Qun
dc.contributor.author Wannemeuhler, Michael
dc.contributor.author Ellinwood, N. Matthew
dc.contributor.author Snella, Elizabeth
dc.contributor.author Martin, Martin
dc.contributor.author Skala, Melissa
dc.contributor.author Meyerholz, David
dc.contributor.author Estes, Mary
dc.contributor.author Fernandez-Zapico, Martin
dc.contributor.author Jergens, Albert
dc.contributor.author Mochel, Jonathan
dc.contributor.author Allenspach, Karin
dc.contributor.department Biomedical Sciences
dc.contributor.department Animal Science
dc.contributor.department Veterinary Clinical Sciences
dc.contributor.department Veterinary Microbiology and Preventive Medicine
dc.contributor.department Chemical and Biological Engineering
dc.date 2020-01-30T18:09:54.000
dc.date.accessioned 2020-06-30T00:53:38Z
dc.date.available 2020-06-30T00:53:38Z
dc.date.copyright Tue Jan 01 00:00:00 UTC 2019
dc.date.issued 2019-04-11
dc.description.abstract <p>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.</p> <p>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.</p> <p>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.</p>
dc.description.comments <p>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." <em>BMC Biology</em> 17 (2019): 33. DOI: <a href="http://dx.doi.org/10.1186/s12915-019-0652-6" target="_blank">10.1186/s12915-019-0652-6</a>. Posted with permission.</p>
dc.format.mimetype application/pdf
dc.identifier archive/lib.dr.iastate.edu/bms_pubs/75/
dc.identifier.articleid 1077
dc.identifier.contextkey 16382296
dc.identifier.s3bucket isulib-bepress-aws-west
dc.identifier.submissionpath bms_pubs/75
dc.identifier.uri https://dr.lib.iastate.edu/handle/20.500.12876/11203
dc.language.iso en
dc.source.bitstream archive/lib.dr.iastate.edu/bms_pubs/75/2019_KimberMichael_DerivationAdult.pdf|||Sat Jan 15 01:49:37 UTC 2022
dc.source.uri 10.1186/s12915-019-0652-6
dc.subject.disciplines Analytical, Diagnostic and Therapeutic Techniques and Equipment
dc.subject.disciplines Digestive System
dc.subject.disciplines Gastroenterology
dc.subject.disciplines Small or Companion Animal Medicine
dc.subject.keywords Organoid model
dc.subject.keywords Canine
dc.subject.keywords Enteroid
dc.subject.keywords GI diseases
dc.subject.keywords Translational research
dc.subject.keywords Intestinal stem cell
dc.title Derivation of adult canine intestinal organoids for translational research in gastroenterology
dc.type article
dc.type.genre article
dspace.entity.type Publication
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