Mesenchymal stem cells administered in the early phase of tumorigenesis inhibit colorectal tumor development in rats

Takayuki Katsuno; Masahiro Ochi; Kazunari Tominaga; Fumio Tanaka; Mitsue Sogawa; Tetsuya Tanigawa; Hirokazu Yamagami; Masatsugu Shiba; Kenji Watanabe; Toshio Watanabe; Yasuhiro Fujiwara; Tetsuo Arakawa

doi:10.3164/jcbn.13-68

Original Articles

Mesenchymal stem cells administered in the early phase of tumorigenesis inhibit colorectal tumor development in rats

Takayuki Katsuno, Masahiro Ochi, Kazunari Tominaga, Fumio Tanaka, Mitsue Sogawa, Tetsuya Tanigawa, Hirokazu Yamagami, Masatsugu Shiba, Kenji Watanabe, Toshio Watanabe, Yasuhiro Fujiwara, Tetsuo Arakawa

Author information

Takayuki Katsuno
Department of Gastroenterology, Osaka City University Graduate School of Medicine
Masahiro Ochi
Department of Internal Medicine, Meijibashi Hospital
Kazunari Tominaga
Department of Gastroenterology, Osaka City University Graduate School of Medicine
Fumio Tanaka
Department of Gastroenterology, Osaka City University Graduate School of Medicine
Mitsue Sogawa
Department of Gastroenterology, Osaka City University Graduate School of Medicine
Tetsuya Tanigawa
Department of Gastroenterology, Osaka City University Graduate School of Medicine
Hirokazu Yamagami
Department of Gastroenterology, Osaka City University Graduate School of Medicine
Masatsugu Shiba
Department of Gastroenterology, Osaka City University Graduate School of Medicine
Kenji Watanabe
Department of Gastroenterology, Osaka City University Graduate School of Medicine
Toshio Watanabe
Department of Gastroenterology, Osaka City University Graduate School of Medicine
Yasuhiro Fujiwara
Department of Gastroenterology, Osaka City University Graduate School of Medicine
Tetsuo Arakawa
Department of Gastroenterology, Osaka City University Graduate School of Medicine

Keywords: mesenchymal stem cell, colorectal tumor, aberrant crypt foci, transforming growth factor β1

JOURNAL FREE ACCESS

2013 Volume 53 Issue 3 Pages 170-175

DOI https://doi.org/10.3164/jcbn.13-68

Details

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.

Corresponding author

Register with J-STAGE for free!