{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T04:47:08Z","timestamp":1764910028344,"version":"3.41.2"},"reference-count":47,"publisher":"The Company of Biologists","issue":"6","license":[{"start":{"date-parts":[[2023,4,27]],"date-time":"2023-04-27T00:00:00Z","timestamp":1682553600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100016469","name":"Takeda Pharmaceuticals International","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100016469","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"crossref","award":["APP1145686"],"award-info":[{"award-number":["APP1145686"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100015539","name":"Australian Government","doi-asserted-by":"crossref","award":["GNT2009049"],"award-info":[{"award-number":["GNT2009049"]}],"id":[{"id":"10.13039\/100015539","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,6,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Patients with Hirschsprung disease lack enteric ganglia in the distal colon and propulsion of colorectal content is substantially impaired. Proposed stem cell therapies to replace neurons require surgical bypass of the aganglionic bowel during re-colonization, but there is inadequate knowledge of the consequences of bypass. We performed bypass surgery in Ednrb\u2212\/\u2212 Hirschsprung rat pups. Surgically rescued rats failed to thrive, an outcome reversed by supplying electrolyte- and glucose-enriched drinking water. Histologically, the bypassed colon had normal structure, but grew substantially less in diameter than the functional region proximal to the bypass. Extrinsic sympathetic and spinal afferent neurons projected to their normal targets, including arteries and the circular muscle, in aganglionic regions. However, although axons of intrinsic excitatory and inhibitory neurons grew into the aganglionic region, their normally dense innervation of circular muscle was not restored. Large nerve trunks that contained tyrosine hydroxylase (TH)-, calcitonin gene-related peptide (CGRP, encoded by Calca or Calcb)-, neuronal nitric oxide synthase (nNOS or NOS1)-, vasoactive intestinal peptide (VIP)- and tachykinin (encoded by Tac1)-immunoreactive axons occurred in the distal aganglionic region. We conclude that the rescued Ednrb\u2212\/\u2212 rat provides a good model for the development of cell therapies for the treatment of Hirschsprung disease.<\/jats:p>","DOI":"10.1242\/dmm.050055","type":"journal-article","created":{"date-parts":[[2023,4,6]],"date-time":"2023-04-06T08:41:20Z","timestamp":1680770480000},"source":"Crossref","is-referenced-by-count":4,"title":["Development of the aganglionic colon following surgical rescue in a cell therapy model of Hirschsprung disease in rat"],"prefix":"10.1242","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0219-3438","authenticated-orcid":false,"given":"John B.","family":"Furness","sequence":"first","affiliation":[{"name":"Florey Institute of Neuroscience and Mental Health 1 , Parkville, Victoria 3010 , Australia"},{"name":"University of Melbourne 2 Department of Anatomy & Physiology , , Parkville, Victoria 3010 , Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enie","family":"Lei","sequence":"additional","affiliation":[{"name":"Florey Institute of Neuroscience and Mental Health 1 , Parkville, Victoria 3010 , Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Billie","family":"Hunne","sequence":"additional","affiliation":[{"name":"Florey Institute of Neuroscience and Mental Health 1 , Parkville, Victoria 3010 , Australia"},{"name":"University of Melbourne 2 Department of Anatomy & Physiology , , Parkville, Victoria 3010 , Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cameron D.","family":"Adams","sequence":"additional","affiliation":[{"name":"Florey Institute of Neuroscience and Mental Health 1 , Parkville, Victoria 3010 , Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alan J.","family":"Burns","sequence":"additional","affiliation":[{"name":"Takeda Pharmaceutical Company International Inc. 3 Gastroenterology Drug Discovery Unit , , Boston, MA 02138 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jill","family":"Wykosky","sequence":"additional","affiliation":[{"name":"Takeda Pharmaceutical Company International Inc. 3 Gastroenterology Drug Discovery Unit , , Boston, MA 02138 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Therese E.","family":"Fazio Coles","sequence":"additional","affiliation":[{"name":"University of Melbourne 2 Department of Anatomy & Physiology , , Parkville, Victoria 3010 , Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linda J.","family":"Fothergill","sequence":"additional","affiliation":[{"name":"Florey Institute of Neuroscience and Mental Health 1 , Parkville, Victoria 3010 , Australia"},{"name":"University of Melbourne 2 Department of Anatomy & Physiology , , Parkville, Victoria 3010 , Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan C.","family":"Molero","sequence":"additional","affiliation":[{"name":"Florey Institute of Neuroscience and Mental Health 1 , Parkville, Victoria 3010 , Australia"},{"name":"University of Melbourne 2 Department of Anatomy & Physiology , , Parkville, Victoria 3010 , Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruslan V.","family":"Pustovit","sequence":"additional","affiliation":[{"name":"Florey Institute of Neuroscience and Mental Health 1 , Parkville, Victoria 3010 , Australia"},{"name":"University of Melbourne 2 Department of Anatomy & Physiology , , Parkville, Victoria 3010 , Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lincon A.","family":"Stamp","sequence":"additional","affiliation":[{"name":"Florey Institute of Neuroscience and Mental Health 1 , Parkville, Victoria 3010 , Australia"},{"name":"University of Melbourne 2 Department of Anatomy & Physiology , , Parkville, Victoria 3010 , Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","published-online":{"date-parts":[[2023,4,27]]},"reference":[{"key":"2023042713204242700_DMM050055C1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1136\/jmg.2007.053959","article-title":"Hirschsprung disease, associated syndromes and genetics: a review","volume":"45","author":"Amiel","year":"2008","journal-title":"J. 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