Marked stem/progenitor cell expansion occurs early after murine ileostomy: a new model

Kathryn L Fowler; Minna M Wieck; Ashley E Hilton; Xiaogang Hou; Christopher R Schlieve; Tracy C Grikscheit

doi:10.1016/j.jss.2017.06.079

Marked stem/progenitor cell expansion occurs early after murine ileostomy: a new model

J Surg Res. 2017 Dec:220:182-196. doi: 10.1016/j.jss.2017.06.079. Epub 2017 Jul 28.

Authors

Kathryn L Fowler¹, Minna M Wieck², Ashley E Hilton³, Xiaogang Hou¹, Christopher R Schlieve², Tracy C Grikscheit⁴

Affiliations

¹ Developmental Biology and Regenerative Medicine Program, The Saban Research Institute at Children's Hospital Los Angeles, Los Angeles, California.
² Developmental Biology and Regenerative Medicine Program, The Saban Research Institute at Children's Hospital Los Angeles, Los Angeles, California; Division of Pediatric Surgery, Department of Surgery, Children's Hospital Los Angeles, Los Angeles, California.
³ Keck Medical School, University of Southern California, Los Angeles, California.
⁴ Developmental Biology and Regenerative Medicine Program, The Saban Research Institute at Children's Hospital Los Angeles, Los Angeles, California; Division of Pediatric Surgery, Department of Surgery, Children's Hospital Los Angeles, Los Angeles, California; Keck Medical School, University of Southern California, Los Angeles, California. Electronic address: tgrikscheit@chla.usc.edu.

PMID: 29180181
DOI: 10.1016/j.jss.2017.06.079

Abstract

Background: Improving treatment for short bowel syndrome requires a better understanding of how intestinal adaptation is affected by factors like mechanoluminal stimulation. We hypothesized that in mice, luminal diversion via an ileostomy would drive adaptive changes similar to those seen in human intestine after diversion while offering the opportunity to study the immediate events after resection that precede intestinal adaptation.

Materials and methods: With Institutional Animal Care and Use Committee approval, a distal ileostomy with a long distal Hartman's was created in 9- to 14-week-old C57/B6 mice (n = 8). Control mice only had a midline laparotomy without stoma formation (n = 5). A rim of tissue from the proximal stoma was resected as a historical control for the proximal segment. Postoperatively, mice received a high-protein liquid diet and water ad libitum. On day 3, tissue from both the proximal and distal limbs were collected for histologic and RNA analysis. Morphometric measures, immunofluorescent antigen detection, and RNA expression were compared with Student paired t-tests with a P value < 0.05 considered significant.

Results: At 3 d, survival for mice with an ileostomy was 87% and average weight loss was 12.5% of initial weight compared to 6.05% for control mice. Compared to the distal limb, the proximal limb in mice with an ileostomy demonstrated significantly taller villi with deeper and wider crypts. The proximal limb also had decreased expression of intestinal stem cell markers lgr5, bmi1, sox9, and ascl2. Fewer goblet and enteroendocrine cells per hemivillus were also noted in the proximal limb. In control mice, none of these measures were significant between proximal and distal ileum except for villus height.

Conclusions: This new murine ileostomy model allows study of intestinal adaptation without intestinal anastomosis, which can be technically challenging and morbid.

Keywords: Ileostomy; Intestinal adaptation; Intestinal stem cell; Mechanoluminal flow; Small intestine; Surgical animal model.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adaptation, Physiological
Adult Stem Cells / physiology*
Animals
Female
Ileostomy*
Intestines / cytology*
Male
Mice
Models, Animal*
Short Bowel Syndrome*