Abstract
Human stem cell-based embryo models (SCBEMs) are a research technology with the potential to facilitate our understanding of human embryogenesis, improve assisted reproductive technology outcomes, elucidate the causes of early pregnancy failure, and provide a clearer understanding of the developmental origins of disease. Given that human SCBEMs are designed to model specific phenotypic features and developmental processes of human embryos, they raise distinct concerns from other stem cell models, such as organoids. The International Society for Stem Cell Research (ISSCR) Guidelines for Stem Cell Research and Clinical Translation, published in 2021, made recommendations for research oversight of SCBEMs and established different categories of review based on involvement of embryonic and extraembryonic lineages. However, recent progress has enabled unexpected ways to create increasingly complex models, as well as more efficient means of doing so without including all major extraembryonic lineages. A working group was tasked by the ISSCR executive to undertake a thorough reexamination of the guidelines in the light of these advances. The three main recommendations of the working group are that all research involving organized 3-dimensional human SCBEMs (1) should be subject to appropriate review, (2) must have a clear scientific rationale, and (3) must be subject to limited timelines. The proposed modifications to the ISSCR guidelines are intended to bring more clarity to the field, help guide the deliberations of researchers, oversight committees and other relevant stakeholders, and ensure continued public confidence.