As research advances in creating structures that mimic human embryos (human embryo models) from iPS cells and ES cells, the regulatory landscape surrounding such research has also begun to change.

In August 2025, the International Society for Stem Cell Research (ISSCR) updated its guidelines for stem cell research and revised the regulations governing research on human embryo models. In the 2021 guidelines, embryo models were classified into two categories: "non-integrated models," which partially mimic development, and "integrated models," which aim to recapitulate the complete developmental process. Integrated models, in particular, were subject to stricter rules, including special review and reporting requirements. In the latest update, however, this distinction was abolished, and a new policy was adopted to monitor all embryo model research uniformly. Why did the ISSCR make this policy shift?

The primary reason is the rapid progress in embryo model research over the past few years. Specifically, even so-called non-integrated models have been reported to exhibit increasingly complex structures and to approach later stages of development. In other words, non-integrated models can no longer be assumed to raise fewer ethical concerns, and the distinction between integrated and non-integrated models has lost much of its practical meaning. While the ISSCR acknowledges that these embryo models are not biologically equivalent to actual human embryos, it judged that, given the difficulty of predicting how far this research may advance, all such models—regardless of type—should be treated comprehensively as SCBEMs (Stem Cell-Based Embryo Models) and subject to uniform oversight.

That said, establishing appropriate rules in a rapidly evolving field like embryo model research poses unique challenges.

Because embryo models are created without the fertilization of sperm and egg, their culture period cannot be managed using criteria such as "days after fertilization." In conventional human embryo research, culture periods have been regulated uniformly based on time elapsed since fertilization—most notably the so-called "14-day rule." However, because embryo models lack fertilization as a clear starting point, regulating them based on elapsed days is unrealistic.

Moreover, while no embryo models currently exist that possess developmental potential equivalent to that of a human embryo, the possibility cannot be entirely ruled out that such models could emerge in the future. In other words, effective rules must be established even though the most critical scientific question—how closely embryo models can approach real human embryos—remains unanswered.

Rules governing research on human embryos and human development have been established in the past, and these were grounded in a mutual understanding among experts regarding scientific facts such as what constitutes a human embryo and what capabilities it possesses. On that basis, discussions were held about the dignity of the human embryo, the value of knowledge gained through research, and the extent to which such research should be permitted. In contrast, embryo models involve a high degree of scientific uncertainty, requiring rules to be formulated for something that is, in many respects, still "unknown." This aspect, arguably, is the distinctive challenge inherent to regulating embryo model research.

• Reference: Questions Raised About Research on Stem Cell-based Human Embryo Models
  (October 27, 2023)