Abstract：
Pluripotency describes the ability of stem cells to differentiate into derivatives of the three germ layers. In reporting new human pluripotent stem cell lines, their clonal derivatives or the safety of differentiated derivatives for transplantation, assessment of pluripotency is essential. Historically, the ability to form teratomas in vivo containing different somatic cell types following injection into immunodeficient mice has been regarded as functional evidence of pluripotency. In addition, the teratomas formed can be analyzed for the presence of malignant cells. However, use of this assay has been subject to scrutiny for ethical reasons on animal use and due to the lack of standardization in how it is used, therefore questioning its accuracy. In vitro alternatives for assessing pluripotency have been developed such as ScoreCard and PluriTest. However, it is unknown whether this has resulted in reduced use of the teratoma assay. Here, we systematically reviewed how the teratoma assay was reported in publications between 1998 (when the first human embryonic stem cell line was described) and 2021. Our analysis of >400 publications showed that in contrast to expectations, reporting of the teratoma assay has not improved: methods are not yet standardized, and malignancy was examined in only a relatively small percentage of assays. In addition, its use has not decreased since the implementation of the ARRIVE guidelines on reduction of animal use (2010) or the introduction of ScoreCard (2015) and PluriTest (2011). The teratoma assay is still the preferred method to assess the presence of undifferentiated cells in a differentiated cell product for transplantation since the in vitro assays alone are not generally accepted by the regulatory authorities for safety assessment. This highlights the remaining need for an in vitro assay to test malignancy of stem cells.
摘要：
多能性描述了干细胞分化成三个胚层衍生物的能力。在报告新的人类多能干细胞系时，它们的克隆衍生物或分化衍生物用于移植的安全性，评估多能性至关重要。历史上,注射入免疫缺陷小鼠后在体内形成包含不同体细胞类型的畸胎瘤的能力被认为是多能性的功能证据。此外,可以分析形成的畸胎瘤是否存在恶性细胞。然而,由于动物使用的伦理原因，并且由于使用方式缺乏标准化，因此该测定法的使用受到了严格的审查，因此质疑其准确性。已经开发了用于评估多能性的体外替代方案,例如ScoreCard和PluriTest。然而,目前尚不清楚这是否导致畸胎瘤试验的使用减少。这里,我们系统回顾了在1998年(首次描述人类胚胎干细胞系)至2021年之间的出版物中如何报道畸胎瘤试验.我们对超过400种出版物的分析表明，与预期相反，畸胎瘤试验的报告没有改善：方法尚未标准化，和恶性肿瘤仅在相对较小百分比的分析中进行检查。此外,自实施ARRIVE关于减少动物使用的指南(2010年)或引入ScoreCard(2015年)和PluriTest(2011年)以来,其使用并未减少.畸胎瘤测定仍然是评估用于移植的分化细胞产物中未分化细胞的存在的优选方法,因为单独的体外测定通常不被监管机构接受用于安全性评估。这突出了对体外测定以测试干细胞的恶性的剩余需要。
