Background
Human embryo models can help researchers study early human development and infertility without relying solely on human embryos. As the technology advances, these models are becoming more complex and can be maintained in culture for longer periods. These developments have raised new questions about how such research should be regulated.
In 2025, the ISSCR revised its guidelines for human embryo model research. Japan followed with revisions to the "Guidelines on the Utilization of Human Embryonic Stem (ES) Cells" and the "Guidelines on Research on Producing Germ Cells from Human-Induced Pluripotent Stem (iPS) Cells or Human Tissue Stem Cells", which came into effect in April 2026. The study examines why these changes were introduced, how the Japanese and ISSCR guidelines differ, and what challenges those differences may create for researchers and institutions.
Methods and Findings
Japan's revised regulations brought all human embryo model research under a single oversight system. This included certain iPS cell-derived embryo model studies that had previously fallen into a regulatory gray area. As a result, all such research now requires ethics review and notification to the national government. The regulations also prohibit transfer into a human or animal uterus and organismal development, require researchers to define the minimum culture period needed for the research in advance, and call for research findings to be made publicly available.
The authors found that the Japanese and ISSCR guidelines are broadly aligned on many key issues. Both require specialized ethical and scientific review, prohibit uterine transfer and organismal development, and emphasize limiting culture periods to what is necessary for the research. However, they differ in how they define human embryo models and what types of research are covered. One notable difference concerns organoid research. The ISSCR guidelines classify some organoid models of human somitogenesis and body-axis formation as human embryo model research, while Japan's guidelines continue to treat organoids and human embryo models as separate categories.
These differences may have practical consequences. Research that is not considered human embryo model research under Japan's regulations may nevertheless be treated as such by international journals and scientific meetings. The authors discuss how researchers, ethics review committees, regulatory authorities, academic societies, and journals can help navigate these differences as expectations and regulations continue to evolve.
Outlook
Advances in human embryo model research are prompting changes in how the field is regulated. As countries revise their regulatory systems at different times and according to different policy approaches, new challenges are likely to emerge for researchers and institutions working across international contexts. Continued dialogue and sharing of experiences across countries will be important to support both scientific progress and public trust.
Researcher's Comment
The idea for this study grew out of conversations with researchers working on human embryo models and our involvement in national discussions on how this research should be regulated. Differences between international and domestic rules can create practical challenges for researchers, ethics review committees, journals, and regulatory authorities. We hope this study helps bring those challenges into focus and encourages discussion among the people responsible for addressing them. Establishing new rules is only part of the challenge. Going forward, the focus will shift to how these rules are interpreted and applied in practice.
Glossary
Human embryo models (stem cell-based embryo models)
Research models created from human embryonic stem (ES) cells or human-induced pluripotent stem (iPS) cells that mimic some or all aspects of human embryonic development. Although distinct from embryos created through fertilization, they are used to investigate early developmental processes and the causes of infertility and miscarriage. They may also provide an alternative to the use of human embryos in research, which can be difficult because of ethical considerations.
Organoids
Three-dimensional cellular structures created from stem cells that replicate certain features of organs such as the brain, intestine, and liver in vitro. Unlike embryo models, which are designed to mimic early developmental processes, organoids are intended to model specific organs or tissues.
