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.

Human pluripotent stem cells (hPSCs) can differentiate into any cell of choice and hold significant promise in regenerative medicine and for treating diseases that currently lack adequate therapies. However, hPSCs are intrinsically tumorigenic and can form teratomas. Therefore, the presence of residual undifferentiated hPSCs must be rigorously assessed using sensitive methodologies to mitigate the potential tumorigenicity risks of hPSC-derived cell therapy products (CTPs). In this comprehensive review, we describe methods for detecting residual undifferentiated hPSCs and discuss the relative value of current in vitro assays versus conventional in vivo assays. We highlight that in vitro assays such as digital PCR detection of hPSC-specific RNA and the highly efficient culture assay, have superior detection sensitivity. Additionally, we outline important considerations for validating in vitro assays when applying them to assess each product. This article lays the groundwork for guiding internationally harmonized procedures for evaluating the potential teratoma formation risk of hPSC-derived CTPs and increasing confidence in the safety of these products.