Mio Kobayashi1,2, Risako Yamashita1, Ryo Ichikawa1, Makoto Shibutani1, Toshinori Yoshida3. 1. Laboratory of Veterinary Pathology, Cooperative Department of Veterinary Medicine, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo, 183-8509, Japan. 2. Cooperative Division of Veterinary Sciences, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo, 183-8509, Japan. 3. Laboratory of Veterinary Pathology, Cooperative Department of Veterinary Medicine, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo, 183-8509, Japan. yoshida7@cc.tuat.ac.jp.
Abstract
BACKGROUND: We previously reported that clumps of a few epithelial cells were scattered in ulcer regions in a dextran sulfate sodium (DSS)-induced mouse model of ulcerative colitis (UC). AIMS: To determine the ectopically localized epithelial clumps might be derived from stem cells or their daughter progenitor cells. METHODS: Female BALB/c mice were administered DSS in drinking water for 6 days, followed by withdrawal of DSS for 6 days. Histological and immunohistochemical examinations were conducted in the distal region and proximal region of the colorectum to determine expression of stem cell markers in the epithelial clumps. RESULTS: Similar to the characteristics of UC, the ulcers were more severe in the distal region close to the anus than in the proximal region of the colorectum. Quantitative analyses revealed that the epithelial clumps appeared in relation to the severity of the ulcer, and they expressed the cell adhesion molecules E-cadherin and β-catenin. Among stem cell markers, the epithelial clumps primarily expressed +5 cell marker Dll1 as reserved intestinal stem cells, followed by +4 cell marker Bmi1 and crypt stem cell marker Lgr5 in that order. Nuclear expression of Sox9, but not nuclear β-catenin, was identified in the clumps. CONCLUSION: The present results suggest that most epithelial clumps comprised crypt-derived, reserved stem cells, which might have potential for mucosal healing.
BACKGROUND: We previously reported that clumps of a few epithelial cells were scattered in ulcer regions in a dextran sulfate sodium (DSS)-induced mouse model of ulcerative colitis (UC). AIMS: To determine the ectopically localized epithelial clumps might be derived from stem cells or their daughter progenitor cells. METHODS: Female BALB/c mice were administered DSS in drinking water for 6 days, followed by withdrawal of DSS for 6 days. Histological and immunohistochemical examinations were conducted in the distal region and proximal region of the colorectum to determine expression of stem cell markers in the epithelial clumps. RESULTS: Similar to the characteristics of UC, the ulcers were more severe in the distal region close to the anus than in the proximal region of the colorectum. Quantitative analyses revealed that the epithelial clumps appeared in relation to the severity of the ulcer, and they expressed the cell adhesion molecules E-cadherin and β-catenin. Among stem cell markers, the epithelial clumps primarily expressed +5 cell marker Dll1 as reserved intestinal stem cells, followed by +4 cell marker Bmi1 and crypt stem cell marker Lgr5 in that order. Nuclear expression of Sox9, but not nuclear β-catenin, was identified in the clumps. CONCLUSION: The present results suggest that most epithelial clumps comprised crypt-derived, reserved stem cells, which might have potential for mucosal healing.
Authors: Fredrik E O Holmberg; Jannie Pedersen; Peter Jørgensen; Christoffer Soendergaard; Kim B Jensen; Ole H Nielsen Journal: J Tissue Eng Regen Med Date: 2017-10-19 Impact factor: 3.963
Authors: Loris R Lopetuso; Carlo De Salvo; Luca Pastorelli; Nitish Rana; Henry N Senkfor; Valentina Petito; Luca Di Martino; Franco Scaldaferri; Antonio Gasbarrini; Fabio Cominelli; Derek W Abbott; Wendy A Goodman; Theresa T Pizarro Journal: Proc Natl Acad Sci U S A Date: 2018-09-17 Impact factor: 11.205