Int J Med Sci 2019; 16(11):1453-1460. doi:10.7150/ijms.35666

Research Paper

Longitudinal micro-endoscopic monitoring of high-success intramucosal xenografts for mouse models of colorectal cancer

Bjorn Paulson1*, Ick Hee Kim2*, Jung-Man Namgoong3*, Young Gyu Kim1, Sanghwa Lee1, Youngjin Moon1,4, Dong-Myung Shin5,6, Myung-Soo Choo7, Jun Ki Kim1,4✉

1. Biomedical Engineering Research Center, Asan Institute for Life Sciences, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 05055, Republic of Korea
2. Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, 391 Technology Way, Winston-Salem, NC 27101, USA
3. Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 05055, Republic of Korea
4. Department of Convergence Medicine, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 05055, Republic of Korea
5. Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 05055, Republic of Korea
6. Department of Physiology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 05055, Republic of Korea
7. Department of Urology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 05055, Republic of Korea
*These authors contributed equally to this work.

Abstract

Colorectal cancer (CRC) is one of the most frequently lethal forms of cancer. Intramucosal injection allows development of better mouse models of CRC, as orthotopic xenografts allow development of adenocarcinoma in the submucosa of the mouse colon wall. In this paper, a method of orthotopic injection is monitored longitudinally using cellular-resolution real-time in vivo fluorescence microendoscopy, following the injection of three different cell lines: 3T3-GFP to confirm immunosuppression and HCT116-RFP cells to model CRC. Adenoma formation is first observable after 7 to 10 days, and by use of 33 G needles a tumor induction rate of greater than 85% is documented. An additional experiment on the injection of rapamycin reveals drug efficacy and localization between 24 and 48 hours, and suggests the promise of real-time cellular-resolution fluorescence micro-endoscopy for developing longitudinal therapy regimes in mural models of CRC.

Keywords: Orthotopic injection, Colorectal cancer, mouse models, microendoscopy, side-view endoscopy, fluorescence imaging

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How to cite this article:
Paulson B, Kim IH, Namgoong JM, Kim YG, Lee S, Moon Y, Shin DM, Choo MS, Kim JK. Longitudinal micro-endoscopic monitoring of high-success intramucosal xenografts for mouse models of colorectal cancer. Int J Med Sci 2019; 16(11):1453-1460. doi:10.7150/ijms.35666. Available from http://www.medsci.org/v16p1453.htm