Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
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TY - JOUR
T1 - Expansion of intestinal stem cells associated with long-term adaptation following ileocecal resection in mice
AU - Dekaney, Christopher M.
AU - Fong, Jerry J.
AU - Rigby, Rachael J.
AU - Lund, P. Kay
AU - Henning, Susan J.
AU - Helmrath, Michael A.
PY - 2007/11
Y1 - 2007/11
N2 - 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.
AB - 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.
KW - intestinal stem cells
KW - intestinal resection
KW - crypt fission
KW - label retention
KW - SMALL-BOWEL RESECTION
KW - TRANSGENIC MICE
KW - BETA-CATENIN
KW - MOUSE
KW - EPITHELIUM
KW - RAT
KW - PROLIFERATION
KW - HYPERPLASIA
KW - GROWTH
KW - CRYPT
U2 - 10.1152/ajpgi.00218.2007
DO - 10.1152/ajpgi.00218.2007
M3 - Journal article
VL - 293
SP - G1013-G1022
JO - American Journal of Physiology-Gastrointestinal and Liver Physiology
JF - American Journal of Physiology-Gastrointestinal and Liver Physiology
SN - 0193-1857
IS - 5
ER -