title: Small intestinal stem cell identity is maintained with functional Paneth cells in heterotopically grafted epithelium onto the colon.
abstract: To develop stem cell therapy for small intestinal (SI) diseases, it is essential to determine whether SI stem cells in culture retain their tissue regeneration capabilities. By using a heterotopic transplantation approach, we show that cultured murine SI epithelial organoids are able to reconstitute self-renewing epithelia in the colon. When stably integrated, the SI-derived grafts show many features unique only to the SI but distinct from the colonic epithelium. Our study provides evidence that cultured adult SI stem cells could be a source for cell therapy of intestinal diseases, maintaining their identity along the gastrointestinal tract through an epithelium-intrinsic mechanism.
authors.affiliation: Department of Gastroenterology and Hepatology.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Fukuda
authors.affiliation: Department of Gastroenterology and Hepatology.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Mizutani
authors.affiliation: Department of Gastroenterology and Hepatology.
authors.forename: Wakana
authors.initials: W
authors.lastname: Mochizuki
authors.affiliation: Department of Gastroenterology and Hepatology.
authors.forename: Taichi
authors.initials: T
authors.lastname: Matsumoto
authors.affiliation: Department of Gastroenterology and Hepatology.
authors.forename: Kengo
authors.initials: K
authors.lastname: Nozaki
authors.affiliation: Research Center for Medical and Dental Sciences.
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Sakamaki
authors.affiliation: Research Center for Medical and Dental Sciences.
authors.forename: Shizuko
authors.initials: S
authors.lastname: Ichinose
authors.affiliation: Department of Human Genetics and Disease Diversity, Bioresource Research Center.
authors.forename: Yukinori
authors.initials: Y
authors.lastname: Okada
authors.affiliation: Department of Human Genetics and Disease Diversity, Bioresource Research Center.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Department of Gastroenterology and Hepatology.
authors.forename: Mamoru
authors.initials: M
authors.lastname: Watanabe
authors.affiliation: Department of Advanced Therapeutics for GI Diseases, Tokyo Medical and Dental University, 113-8519 Tokyo, Japan nakamura.gast@tmd.ac.jp.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Nakamura
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003106:Colon / Q000166:cytology* / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000637:transplantation*; D004848:Epithelium / Q000378:metabolism / Q000648:ultrastructure; D007421:Intestine, Small / Q000166:cytology* / Q000378:metabolism; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D009940:Organoids / Q000166:cytology; D019879:Paneth Cells / Q000166:cytology* / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D059467:Transcriptome; D016042:Transplantation, Heterotopic
keywords: Paneth cell; regenerative medicine; small intestinal stem cell; stem cell niche; transplantation