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This Article Full Text Full Text (PDF) All Versions of this Article: 293/5/G1013    most recent 00218.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Dekaney, C. M. Articles by Helmrath, M. A. Search for Related Content PubMed PubMed Citation Articles by Dekaney, C. M. Articles by Helmrath, M. A.

MUCOSAL BIOLOGY

Expansion of intestinal stem cells associated with long-term adaptation following ileocecal resection in mice

Departments of ¹Surgery, ²Medicine, and ³Cell and Molecular Physiology, University of North Carolina, Chapel Hill, North Carolina; and ⁴Michael E. DeBakey Department of Surgery and Departments of ⁵Pediatrics and ⁶Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas

Submitted 16 May 2007 ; accepted in final form 12 September 2007

Sustained increases in mucosal surface area occur in remaining bowel following massive intestinal loss. The mechanisms responsible for expanding and perpetuating this response are not presently understood. We hypothesized that an increase in the number of intestinal stem cells (ISC) occurs following intestinal resection and is an important component of the adaptive response in mice. This was assessed in the jejunum of mice 2–3 days, 4–5 days, 6–7 days, 2 wk, 6 wk, and 16 wk following ileocecal resection (ICR) or sham operation. Changes in ISC following ICR compared with sham resulted in increased crypt fission and were assayed by 1) putative ISC population (SP) by flow cytometry, 2) Musashi-1 immunohistochemistry, and 3) bromodeoxyuridine (BrdU) label retention. Observed early increases in crypt depth and villus height were not sustained 16 wk following operation. In contrast, long-term increases in intestinal caliber and overall number of crypts per circumference appear to account for the enhanced mucosal surface area following ICR. Flow cytometry demonstrated that significant increases in SP cells occur within 2–3 days following resection. By 7 days, ICR resulted in marked increases in crypt fission and Musashi-1 immunohistochemistry staining. Separate label-retention studies confirmed a 20-fold increase in BrdU incorporation 6 wk following ICR, confirming an overall increase in the number of ISC. These studies support that expansion of ISC occurs following ICR, leading to an overall increase number of crypts through a process of fission and intestinal dilation. Understanding the mechanism expanding ISCs may provide important insight into management of intestinal failure.

intestinal stem cells; intestinal resection; crypt fission; label retention

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