Pluripotent stem cells offer the potential for an unlimited source for cell therapy products. However, there is concern regarding the tumorigenicity of these products in humans, mainly due to the possible unintended contamination of undifferentiated cells or transformed cells. Because of the complex nature of these new therapies and the lack of a globally accepted consensus on the strategy for tumorigenicity evaluation, a case-by-case approach is recommended for the risk assessment of each cell therapy product. In general, therapeutic products need to be qualified using available technologies, which ideally should be fully validated. In such circumstances, the developers of cell therapy products may have conducted various tumorigenicity tests and consulted with regulators in respective countries. Here, we critically review currently available in vivo and in vitro testing methods for tumorigenicity evaluation against expectations in international regulatory guidelines. We discuss the value of those approaches, in particular the limitations of in vivo methods, and comment on challenges and future directions. In addition, we note the need for an internationally harmonized procedure for tumorigenicity assessment of cell therapy products from both regulatory and technological perspectives.

中文翻译：

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细胞治疗产品的致瘤性评估：需要全球共识和考虑要点

多能干细胞为细胞治疗产品的无限来源提供了潜力。然而，人们担心这些产品在人类中的致瘤性，主要是由于未分化细胞或转化细胞可能会意外污染。由于这些新疗法的复杂性以及对致瘤性评估策略缺乏全球公认的共识，建议对每种细胞疗法产品的风险评估采用逐案方法。一般而言，治疗产品需要使用现有技术进行认证，理想情况下应充分验证。在这种情况下，细胞治疗产品的开发者可能已经进行了各种致瘤性测试，并咨询了各自国家的监管机构。这里，我们严格审查了目前可用的体内和体外测试方法，以对照国际监管指南中的预期进行致瘤性评估。我们讨论了这些方法的价值，特别是体内方法的局限性，并评论了挑战和未来的方向。此外，我们注意到需要从监管和技术角度对细胞治疗产品进行致瘤性评估的国际统一程序。