The goal, the scientists involved in the study said, is not to create mice or babies outside the womb, but to begin to understand how organs develop in embryos and use that knowledge to develop new ways to treat people.
From a pool of embryonic stem cells, scientists at the Weizmann Institute of Science created synthetic embryos that closely resembled real mouse embryos, with a rudimentary beating heart, circulation, wrinkled brain tissue and an intestinal tract. Mouse embryos grow in an artificial womb and stop developing after eight days, about a third of a mouse’s pregnancy.
The advance, a decade in the making, arrives in a field crowded with efforts to develop embryonic models from human and mouse cells. Scientists can use such models to peer into the earliest stages of embryonic development and study how organs form.
But as models come closer to the real thing, they also open up ethically murky territory. At what point do synthetic embryos become so similar to real embryos that they become subject to protections similar to those applied to real embryos?
“This is an important landmark in our understanding of how embryos build themselves,” Alfonso Martínez Arias, a developmental biologist at Pompeu Fabra University in Barcelona who was not involved in the research, said in an email. He called the experiment a “game changer.”
The research, published Monday in the journal Cell, is a far cry from growing a mouse, much less a human, outside the womb. It was a proof of concept that a complete synthetic embryo could be assembled from embryonic stem cells, and while the researchers succeeded, it was a highly error-prone process, with only a small proportion of embryos going on to develop the beginnings of a beating heart and other organs .
Although the synthetic mouse embryos bore a strong resemblance to natural mouse embryos, they were not exactly the same and did not implant or lead to pregnancy in real mice, according to Jacob Hanna, a stem cell scientist at the Weizmann Institute of Science who led the research work.
“This is an interesting next step, not shocking, but one that makes more plausible in the long run a proposal with far-reaching implications: the possibility of turning any mouse cell into a living mouse,” Henry T. Greeley, a bioethicist at Stanford Law School , said.
The study, like other recent studies, puts the possibility of a fully human synthetic embryo on the horizon, several researchers said, prompting continued public discussion about how these entities should be handled. Last year, the International Society for Stem Cell Research relaxed a historic “14-day rule” under which researchers can grow natural embryos for just 14 days in a lab, allowing researchers to seek approval for longer studies. Human embryo models are prohibited for implantation in the uterus.
“The mouse is a starting point for thinking about how one wants to approach this in humans,” said Alex Meissner, a stem cell biologist at the Max Planck Institute for Molecular Genetics. “There’s no need to worry or panic, but … as we’re learning, it’s important to have a parallel discussion: How far do we want to go?”
Hanna said his hope is that the technology can be used not as a replacement for reproduction, but as a way to create synthetic models of human embryos that can lead to organ precursors that can be studied and potentially used therapeutically. .
For decades, the main hope for stem cell therapy has been to regenerate the body’s own tissues. Stem cells can develop into any tissue or organ, so the potential to use these cells to repair spinal cord injuries, patch together damaged hearts or treat diabetes is tantalizing. But turning these cells into complex, functioning tissue is a challenge. Hanna’s hope is that observing this process during early development will provide important clues.
“Our goal is not to get pregnant outside the uterus, whether it’s in mice or other species,” Hanna said. “We are really facing difficulties in making organs – and to get stem cells to become organs, we need to learn how the embryo does that. We started with this because the uterus is a black box – it is not transparent.
Hannah has founded Renewal Bio, a company that plans to use the technology therapeutically. One possible use would be to take skin cells from a woman with fertility problems, reprogram those skin cells to create stem cells, and then grow synthetic embryo models that can be used to produce eggs.