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Small intestinal stem cell identity is maintained with functional Paneth cells in heterotopically grafted epithelium onto the colon
Authors:Masayoshi Fukuda  Tomohiro Mizutani  Wakana Mochizuki  Taichi Matsumoto  Kengo Nozaki  Yuriko Sakamaki  Shizuko Ichinose  Yukinori Okada  Toshihiro Tanaka  Mamoru Watanabe  Tetsuya Nakamura
Affiliation:1.Department of Gastroenterology and Hepatology.;2.Research Center for Medical and Dental Sciences.;3.Department of Human Genetics and Disease Diversity.;4.Bioresource Research Center.;5.Department of Advanced Therapeutics for GI Diseases, Tokyo Medical and Dental University, 113-8519 Tokyo, Japan
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.
Keywords:small intestinal stem cell   transplantation   stem cell niche   Paneth cell   regenerative medicine
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