Abstract
In recent years, a positive control group is frequently included in tumorigenicity studies using an immunodeficient animal model for regenerative medical products. However, few cell lines have been investigated in detail and recommended to take a role of a positive control in tumorigenicity studies of an intravenous route. This study was conducted to explore whether the human neuroblastoma-derived SK-N-SH cell line can be utilized as a positive control for intravenous tumorigenicity studies.
The SK-N-SH cells were intravenously administrated once to 10 females NOG mice (NOD/Shi-scid, IL-2RγKOJic) each at 7 weeks old at 7.8x102, 7.8x103 and 7.8x104 cells/mouse, respectively, and the animals were observed for 16 weeks thereafter.
All the animals died during Week 8-14 in the 7.8x103 and 7.8x104 cells/mouse groups and three animals during Week 12-14 in the 7.8x102 cells/mouse group because of the colonization of the SK-N-SH cells in various organs, primarily in the liver. The 50% tumor-producing dose (TPD50) was determined to be 909 cells/mouse on the basis of hepatic colonization ratio.
In conclusion, the human neuroblastoma-derived SK-N-SH cell line is valid to play a role of a positive control cell in intravenous tumorigenicity studies at three dosing levels used in this study, and an adequate number of cells were proposed in accordance to the study period.
