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Given that CD44 variant isoform 9 (CD44v9) is expressed within Spasmolytic Polypeptide\/TFF2\u2010Expressing Metaplasia (SPEM) glands during repair, CD44v9 may be play a funcitonal role during the process of regeneration of the gastric epithelium. Here we hypothesize that CD44v9 marks a regenerative cell lineage responsive to infiltrating macrophages during regeneration of the gastric epithelium. Ulcers were induced in CD44\u2010deficient (CD44KO) and C57BL\/6 (BL6) mice by a localized application of acetic acid to the serosal surface of the stomach. Gastric organoids expressing CD44v9 were derived from mouse stomachs and transplanted at the ulcer site of CD44KO mice. Ulcers, CD44v9 expression, proliferation and histology were measured 1, 3, 5 and 7\u2010days post\u2010injury. Human\u2010derived gastric organoids were generated from stomach tissue collected from elderly (&gt;55 years) or young (14\u201320 years) patients. Organoids were transplanted into the stomachs of NOD scid gamma (NSG) mice at the site of injury. Gastric injury was induced in NRG\u2010SGM3 (NRGS) mice harboring human\u2010derived immune cells (hnNRGS) and the immune profile anlayzed by CyTOF. CD44v9 expression emerged within regenerating glands the ulcer margin in response to injury. While ulcers in BL6 mice healed within 7\u2010days post\u2010injury, CD44KO mice exhibited loss of repair and epithelial regeneration. Ulcer healing was promoted in CD44KO mice by transplanted CD55v9\u2010expressing gastric organoids. NSG mice exhibited loss of CD44v9 expression and gastric repair. Transplantation of human\u2010derived gastric organoids from young, but not aged stomachs promoted repair in NSG mouse stomachs in response to injury. Finally, compared to NRGS mice, huNRGS animals exhibited reduced ulcer sizes, an infiltration of human CD162+ macrophages and an emergence of CD44v9 expression in SPEM. Thus, during repair of the gastic epithelium CD44v9 emerges within a regenerative cell lineage that coincides with macrophage inflitration within the injured mucosa. Copyright \u00a9 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/path.4918","type":"journal-article","created":{"date-parts":[[2017,5,12]],"date-time":"2017-05-12T03:32:44Z","timestamp":1494559964000},"page":"463-475","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["CD44 variant isoform 9 emerges in response to injury and contributes to the regeneration of the gastric epithelium"],"prefix":"10.1002","volume":"242","author":[{"given":"Nina","family":"Bertaux\u2010Skeirik","sequence":"first","affiliation":[{"name":"Department of Molecular and Cellular Physiology University of Cincinnati  Cincinnati OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Wunderlich","sequence":"additional","affiliation":[{"name":"Cancer and Blood Disease Institute, Experimental Hematology and Cancer Biology Cincinnati Children's Hospital Medical Center  Cincinnati OH 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