کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2022335 1542365 2015 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Characterization of in vivo tumorigenicity tests using severe immunodeficient NOD/Shi-scid IL2Rγnull mice for detection of tumorigenic cellular impurities in human cell-processed therapeutic products
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Characterization of in vivo tumorigenicity tests using severe immunodeficient NOD/Shi-scid IL2Rγnull mice for detection of tumorigenic cellular impurities in human cell-processed therapeutic products
چکیده انگلیسی


• The tumorigenicity tests using NOG mice (NOG) were characterized, by using HeLa cells (HeLa) as a positive control.
• NOG showed 30-fold higher sensitivity to HeLa, compared with nude mice (Nude) recommended in the WHO TRS 878 guideline.
• A combination of NOG and Matrigel (MG) showed 5000-fold higher sensitivity to HeLa, compared with Nude without MG.
• The NOG-MG combination detected as low as 0.0001% HeLa cells in human somatic stem cells (hMSCs) at a probability of 17%.
• The tumorigenicity test using NOG and MG is useful to detect tumorigenic impurities of cell-processed therapeutic products.

The contamination of human cell-processed therapeutic products (hCTPs) with tumorigenic cells is one of the major concerns in the manufacturing and quality control of hCTPs. However, no quantitative method for detecting the tumorigenic cellular impurities is currently standardized. NOD/Shi-scid IL2Rγnull (NOG) mice have shown high xeno-engraftment potential compared with other well-known immunodeficient strains, e.g. nude mice. Hypothesizing that tumorigenicity test using NOG mice could be a sensitive and quantitative method to detect a small amount of tumorigenic cells in hCTPs, we examined tumor formation after subcutaneous transplantation of HeLa cells, as a model of tumorigenic cells, in NOG mice and nude mice. Sixteen weeks after inoculation, the 50% tumor-producing dose (TPD50) values of HeLa cells were stable at 1.3 × 104 and 4.0 × 105 cells in NOG and nude mice, respectively, indicating a 30-fold higher sensitivity of NOG mice compared to that of nude mice. Transplanting HeLa cells embedded with Matrigel in NOG mice further decreased the TPD50 value to 7.9 × 10 cells, leading to a 5000-fold higher sensitivity, compared with that of nude mice. Additionally, when HeLa cells were mixed with 106 or 107 human mesenchymal stem cells as well as Matrigel, the TPD50 values in NOG mice were comparable to those of HeLa cells alone with Matrigel. These results suggest that the in vivo tumorigenicity test using NOG mice with Matrigel is a highly sensitive and quantitative method to detect a trace amount of tumorigenic cellular impurities in human somatic cells, which can be useful in the quality assessment of hCTPs.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Regenerative Therapy - Volume 1, June 2015, Pages 30–37
نویسندگان
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