Research involving human embryos is famously difficult and fraught with ethical quandaries, but a new synthetically derived model could open new doors in the study of infertility and birth defects.
The model comes from the Weizmann Institute of Science in Israel and follows years of research by labs around the world into producing a similar clump of cells. The team led by professor Jacob Hanna claims that their latest iteration is the most advanced so far and contains all the hallmarks of a human embryo that has grown inside a human womb for 14 days.
The advancement raises a host of ethical questions that the scientific world is just beginning to grapple with.
Scientists generally agree that experiments involving embryos should halt at 14 days, when major features such as the body shape and spinal cord begin to form. But most of the related scientific guidelines and national laws only apply to embryos derived from fertilized human eggs, not synthetic ones like Hanna’s.
Little is known about the early days of the human embryo, during which it develops all the organs needed to sustain human life.
“That first month is still largely a black box,” said Hanna in a statement. “Our complete stem-cell derived human embryo model offers an ethical and accessible way of peering into this box.”
To develop their unique clump of cells, Hanna’s team took stem cells from human skin and preexisting cultures and reverted them to a blank or “naïve” state. This aligned them with the cells generally found inside a seven-day-old embryo, at the time when it embeds itself in the womb.
The team divided the loose cells into several groups and treated each with a chemical to turn on certain genes (with the exception of the core embryo cells, which remained as-is). One group of cells became placenta cells, while another type was needed for the yolk sac. The last group became an early version of chorionic sac cells, which help to encase the embryo.
Then, under special conditions, the researchers mixed all the cells together and formed clumps, like cellular oatmeal. The team looked closer and found that in 1 percent of cases, the clumps had formed tiny embryo-like structures.
“An embryo is self-driven by definition,” said Hanna. “We don’t need to tell it what to do. We must only unleash its internally encoded potential.”
He dubbed the structures “stem cell-based complete embryo-like structures (SEMs)” and fostered their development for eight days, until they had reached the equivalent of 14 days of normal development. Along the way, his team found that the SEMs bore a close resemblance to the embryos illustrated in classical embryology atlases from the 1960s.
“Every compartment and supporting structure was not only there but in the right place, size and shape,” the statement said.
When the researchers extracted secretions from SEM and applied them to a commercial pregnancy test, it read positive.
Potential uses for SEMs range from studying the earliest stages of pregnancies – when many fail – to growing new transplant tissues and organs. The structures may also serve as an ethical workaround for certain experiments, allowing researchers to tread in areas not otherwise possible with traditional embryos. One possible avenue could involve testing the effects of drugs (pharmaceutical or otherwise) on a developing SEM.
Hanna’s paper comes at time when the field of embryonic research is reconsidering the old 14-day standard, although it remains legally enforced in many countries. In 2021, the influential International Society for Stem Cell Research relaxed its old 14-day guideline and instead encouraged scientists to have a public conversation about what is an appropriate standard.
The organization has forbidden scientists from implanting model human embryos, such as SEMs, in the wombs of animals or humans. Doing the latter would essentially be an act of human cloning, which is banned in some 45 countries around the world.