Mesenchymal stem cells administered in the early phase of tumorigenesis inhibit colorectal tumor development in rats
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- Katsuno Takayuki
- Department of Gastroenterology, Osaka City University Graduate School of Medicine
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- Ochi Masahiro
- Department of Internal Medicine, Meijibashi Hospital
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- Tominaga Kazunari
- Department of Gastroenterology, Osaka City University Graduate School of Medicine
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- Tanaka Fumio
- Department of Gastroenterology, Osaka City University Graduate School of Medicine
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- Sogawa Mitsue
- Department of Gastroenterology, Osaka City University Graduate School of Medicine
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- Tanigawa Tetsuya
- Department of Gastroenterology, Osaka City University Graduate School of Medicine
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- Yamagami Hirokazu
- Department of Gastroenterology, Osaka City University Graduate School of Medicine
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- Shiba Masatsugu
- Department of Gastroenterology, Osaka City University Graduate School of Medicine
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- Watanabe Kenji
- Department of Gastroenterology, Osaka City University Graduate School of Medicine
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- Watanabe Toshio
- Department of Gastroenterology, Osaka City University Graduate School of Medicine
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- Fujiwara Yasuhiro
- Department of Gastroenterology, Osaka City University Graduate School of Medicine
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- Arakawa Tetsuo
- Department of Gastroenterology, Osaka City University Graduate School of Medicine
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Abstract
To investigate the differences between the effects of mesenchymal stem cells (MSCs) administered in the early and late phases of tumorigenesis, MSCs were isolated from bone marrow and colorectal tumors were produced by exposing 7-week-old F344 rats to 1,2-dimethylhydrazine and dextran sulfate sodium. We evaluated tumor number and volume (week 25), MSC localization, number of aberrant crypt foci (ACF), transforming growth factor (TGF)-β1 protein levels in the rectum after administration of MSCs (week 5 or 15), and the effects of MSC-conditioned medium on ACL15 cell proliferation. Administered MSCs labeled with PKH26 were observed in the rectum. Administered MSCs in the early phase (week 5) before tumor occurrence (week 12) significantly decreased tumor number and volume (1.5 vs 4 and 21 mm3 vs 170 mm3; p<0.01), but not administered MSCs in the late phase (week 15). Administered MSCs in the early phase reduced ACF number on days 14 and 35 (1.9 vs 4.1 and 3.7 vs 7.3; p<0.01). Rectal TGF-β1 increased 1.3 fold on day 3, and MSC-conditioned medium containing TGF-β1 abundantly inhibited ACL15 cell proliferation. MSCs administered in the early phase but not late phase inhibited colorectal tumor development in a rat model.
Journal
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- Journal of Clinical Biochemistry and Nutrition
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Journal of Clinical Biochemistry and Nutrition 53 (3), 170-175, 2013
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