Evaluating teratoma formation risk of pluripotent stem cell-derived cell therapy products: a consensus recommendation from the Health and Environmental Sciences Institute’s International Cell Therapy Committee

The CGT-TRACS Committee has published a position paper in Cytotherapy that provides consensus expert recommendations on evaluating teratoma formation risk in human pluripotent stem cell (hPSC)-derived cell therapy products.

This paper follows the first and widely cited output from this HESI committee (Sato et al. 2019), integrating learnings from its work since then and current state of the science on the topic.

Pluripotent stem cells offer immense promise to treat conditions that lack effective therapies. However, their ability to form teratomas, a type of tumor composed of multiple tissue types, poses a significant safety concern when residual undifferentiated cells remain in the final cell therapy product. Current regulatory frameworks require rigorous safety assessments, typically including in vivo tumorigenicity assays. However, the translational relevance of traditional in vivo assays for cell-based therapies is debated, as these models presuppose that human cells will exhibit comparable behavior in animal hosts and in the human physiological environment.

This publication:

• Reviews the limitations of traditional in vivo teratoma assays.
• Compares emerging in vitro methods such as droplet digital PCR (dPCR) and highly efficient culture (HEC) assays.
• Presents findings from multi-site validation studies showing these in vitro approaches offer significantly greater sensitivity and reproducibility than current in vivo methods.
• Provides practical guidance for integrating these assays into product quality control frameworks.
• This consensus paper represents a significant advancement toward the global harmonization of tumorigenicity assessment in regenerative medicine. It supports HESI Global’s mission to resolve global health challenges through collaborative science, and it equips developers and regulators with robust tools to enhance the safety of next-generation cell therapies.

Read the full paper here:

Watanabe et al. 2025. Evaluating teratoma formation risk of pluripotent stem cell-derived cell therapy products: a consensus recommendation from the Health and Environmental Sciences Institute’s International Cell Therapy Committee. Cytotherapy, DOI: 10.1016/j.jcyt.2025.04.062