Intestinal Epithelial Stem Cells: Distinct Behavior After Surgical Injury and Teduglutide Administration.

BACKGROUND

Previous studies suggest that intestinal epithelial stem cells (IESC), critical drivers of homeostasis and regeneration, include two subpopulations: crypt-based columnar and "position +4" stem cells, identified by Lgr5 and Bmi1 biomarkers, respectively. Teduglutide is an enterotrophic counterpart of glucagon-like peptide 2. This study aimed to investigate the response of putative IESC to surgical injury and teduglutide administration on an animal model of intestinal resection and anastomosis.

METHODS

Wistar rats (n = 59) were distributed into four groups: "Ileal Resection" versus "Laparotomy", subsequently subdivided into "Postoperative Teduglutide Administration" versus "No Treatment"; and sacrificed at third or seventh days, with ileal sample harvesting. Flow cytometry was used to analyze epithelial stem cells with monoclonal antibodies against Lgr5, Bmi1 and also CD44, CD24, CD166, and Grp78 surface markers.

RESULTS

Surgical trauma induced an increase of epithelial stem cells population at third day (9.0 ± 0.3 versus 5.7 ± 0.3%, p = 0.0001), which was more intense and involved all subpopulations after ileal resection. At seventh day, teduglutide was significantly associated with higher proportion of Lgr5/Bmi1 cells (5.8 ± 0.1 versus 2.9 ± 0.3%, p = 0.005) and, on the contrary, lower percentage of Lgr5/Bmi1 cells (0.03 ± 0.01 versus 1.9 ± 0.1%, p = 0.049) after ileal resection; and higher proportion of Lgr5/Bmi1 cells (1.7 ± 0.1 versus 1.1 ± 0.2%, p = 0.028) after isolated laparotomy. After surgery, Lgr5/Bmi1 and Lgr5/Bmi1 subpopulations demonstrated an inverse correlation and both correlated negatively with Grp78 labeling index. Lgr5/Bmi1 and CD44/CD24/CD166/Grp78 cells proportions exhibited a high grade positive correlation.

CONCLUSION

Those observations support the existence of two epithelial stem cells subpopulations with distinct behavior after surgical injury and teduglutide treatment.