Human embryo research is a challenging field – ethically, scientifically, and legally. The “14-day rule,” established in 1990, is a widely adopted limit prohibiting in vitro research on human embryos beyond 14 days post-fertilization. Recently developed stem cell-based embryo models may reduce (but cannot entirely substitute for) the use of donated embryos created by IVF, but the most advanced of these models are similarly limited to around 14 days. In December, the UK national fertility regulator recommended that the government extend the length of time for which human embryos can be grown in culture to 28 days post-fertilization. This would enable scientists to study, for instance, the start of organ development, revealing insights into congenital heart, musculoskeletal, or spinal-cord conditions. At 28 days, the embryo still hasn’t developed neurons, so cannot sense or feel anything.
While the myriad issues are debated, the period between 14 and 28 days remains the “black box” of human development. However, a paper in the current issue of Cell goes some way to changing that, albeit focusing on extra-embryonic tissues, i.e., tissues that develop alongside the embryo but are not incorporated into its final body structure. The authors present “post-gastrulation amnioids” (PGAs), which model the amniotic sac (the fluid-filled sac surrounding the embryo) and other extra-embryonic tissues at weeks 2–4. PGAs represent the first model to recapitulate aspects of human development after day 14.
As well as enabling researchers to study amnion formation, signaling, and function, PGAs have direct medical potential: the amniotic membrane (which has regenerative, anti-inflammatory, and antimicrobial properties) can be used to treat various eye conditions, and even burns or other skin wounds.
Post-gastrulation amnioids as a stem cell-derived model of human extra-embryonic development
In Cell, 10 July 2025
From the group of Silvia Santos at The Francis Crick Institute
Snippet by Katrina Woolcock
Image credit: graphical abstract from Gharibi et al. cited above (CC BY 4.0), cropped to remove white space