Characteristics of Colon Crypt Stem Cells in Preserved Epithelial Cell Clumps in Dextran Sulfate Sodium-induced Mouse Model of Ulcerative Colitis

Crypt stem cells rescue the colorectum from refractory ulcers in ulcerative colitis (UC). 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 UC; however, the origin of the clumps is unknown. We determined the immunohistochemical expression of stem-cell markers in the epithelial clumps in female Balb/c mice administered DSS in drinking water for 6 days, followed by withdrawal of DSS for 6 days. 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 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, followed by + 4 cell marker Bmi1 and crypt stem cell marker Lgr5 in that order. Nuclear expression of Sox9, but not Ki-67 and β-catenin was identified in the clumps. The present results suggest that the epithelial clumps comprised crypt-derived stem cells with the potential to regenerate crypts, which could serve as a potential treatment strategy for UC.