Higher susceptibility of NOG mice to xenotransplanted tumors
Higher susceptibility of NOG mice to xenotransplanted tumors
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DOI：
10.2131/jts.34.123
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发表时间：
2009-02-01
影响因子：
2
通讯作者：
Tsuchiya, Toshie
中科院分区：
文献类型：
--
作者：
Machida, Kazuhiko;Suemizu, Hiroshi;Tsuchiya, Toshie
致瘤性试验的目的不仅适用于用于病毒疫苗生产的细胞基质，而且适用于用于细胞治疗的干细胞，其目的是区分具有形成肿瘤能力的细胞和不具有形成肿瘤能力的细胞。因此，致瘤性试验在评估这些生物材料的安全性方面至关重要。最近开发的NOD/Shi-scid IL 2 Rg（null）（NOG）小鼠已经显示出对于正常细胞和癌细胞的异种移植优于NOD/Shi-scid（SCID）小鼠上级。为了选择合适的小鼠品系作为致瘤性试验的异种宿主，我们比较了NOG（T、B和NK细胞缺陷型）、SCID（T和B细胞缺陷型）和传统使用的裸鼠（T细胞缺陷型）对异种移植HeLa S3细胞肿瘤形成的易感性。当101个HeLa S3细胞皮下接种到这些小鼠的侧腹时，第22天的肿瘤发生率在NOG中为10/10（100%），在SCID中为2/10（20%），在裸鼠中为0/10（0%）。皮下肿瘤以剂量依赖性方式可重复和半定量地形成。出乎意料的是，仅接种了10（1）个HeLa S3细胞的NOG小鼠中的一半（5/10）在第78天形成了进行性生长的皮下肿瘤。我们证实，移植的肿瘤来源于接种的HeLa S3细胞免疫组化染色与抗HLA抗体。提示NOG小鼠可能是检测致瘤性的最佳品系。
The purpose of tumorigenicity testing, as applied not only to cell Substrates used for viral vaccine manufacture but also stem cells used for cell-based therapy, is to discriminate between cells that have the capacity to form tumors and cells that do not. Therefore, tumorigenicity testing is essential in assessing the safety of these biological materials. Recently developed NOD/Shi-scid IL2Rg(null) (NOG) mice have been shown to be Superior to NOD/Shi-scid (SCID) mice for xenotransplantation of both normal and cancerous cells. To select a suitable mouse strain as a xenogenic host for tumorigenicity testing, we compared the susceptibility of NOG (T, B, and NK cell-defective), SCID (T and B cell-defective), and the traditionally used nude (T cell-defective) mice to tumor formation from xenotransplanted HeLa S3 cells. When 101 HeLa S3 cells were subcutaneously inoculated into the flanks of these mice, the tumor incidence oil day 22 was 10/10 (100%) in NOG, 2/10 (20%) in SCID, and 0/10 (0%) in nude mice. The subcutaneous tumors formed reproducibly and semiquantitatively in a dose-dependent manner. Unexpectedly, half of the NOG mice (5/10) that had been inoculated with a mere 10(1) HeLa S3 cells formed progressively growing Subcutaneous tumors oil day 78. We confirmed that the engrafted tumors originated from inoculated HeLa S3 cells by immunohistochemical staining with anti-HLA antibodies. These data Suggest that NOG mice may be the best choice as a suitable strain for testing tumorigenicity.