In a groundbreaking development, scientists at the Weizmann Institute of Science successfully created complete synthetic models of human embryos using stem cells grown in a laboratory. The synthetic embryos were nurtured outside the womb and survived up to 14 days of development with all the features characteristic of their stage, even though no sperm or eggs were used.
The Israeli findings, published in the peer-reviewed journal, Nature, hold significant promise for diverse fields such as infertility research, drug testing, tissue transplantation, and a deeper understanding of early embryonic development.
Led by Prof. Jacob Hanna, the Weizmann research team’s embryos were the first to feature vital structures and compartments, including the placenta, yolk sac, chorionic sac, and other external tissues essential for embryonic development and growth.
“Our stem cell–derived human embryo model offers an ethical and accessible way of peering into this box. It closely mimics the development of a real human embryo, particularly the emergence of its exquisitely fine architecture,” Hanna said.
The research builds on Hanna’s prior experience in creating synthetic models of mouse embryos without using fertilized eggs or a womb. Instead, they began with pluripotent stem cells which are capable of differentiating into various cell types. Some of these cells were derived from reprogrammed adult skin cells, while others came from long-cultured human stem cell lines.
Hanna’s team reprogrammed these pluripotent stem cells to revert to an earlier, “naïve” state, similar to day seven of natural human embryo development implanted in the womb. The researchers divided these cells into three groups, targeting their differentiation towards the placenta, yolk sac, or the extraembryonic mesoderm membrane needed for the chorionic sac.
When mixed together under optimized conditions, the cells self-organized into complete embryo-like structures.
“An embryo is self-driven by definition; we don’t need to tell it what to do – we must only unleash its internally encoded potential,” Hanna explained. “It’s critical to mix in the right kinds of cells at the beginning, which can only be derived from naïve stem cells that have no developmental restrictions. Once you do that, the embryo-like model itself says, ‘Go!’”
These stem cell–based embryo-like structures, termed SEMs, developed naturally outside the womb for eight days, equivalent to day 14 in human embryonic development. At this point, natural embryos acquire the internal structures necessary for progressing to the next stage of development, including the formation of body organs.
Remarkably, when compared to classical embryology atlases from the 1960s, the inner organization of the stem cell–derived embryo models exhibited an uncanny structural resemblance to natural human embryos at the corresponding stage. Each compartment, supporting structure, and even the cells responsible for producing pregnancy hormones were accurately replicated, the researchers said.
“Our models can be used to reveal the biochemical and mechanical signals that ensure proper development at this early stage, and the ways in which that development can go wrong,” Hanna said.
One finding of particular significance is the potential to investigate early pregnancy failure. The researchers found that improper envelopment of the embryo by placenta-forming cells at a specific point in the development process led to the failure of internal structures like the yolk sac to develop correctly.
“An embryo is not static. It must have the right cells in the right organization, and it must be able to progress – it’s about being and becoming,” Hanna stressed. “Our complete embryo models will help researchers address the most basic questions about what determines its proper growth.”
The findings open new avenues of research, including identifying causes of birth defects and infertility, developing innovative technologies for growing transplant tissues and organs, and providing an alternative to experiments that cannot be conducted on live embryos, such as studying the effects of drug exposure on fetal development.
