Scientists have created “synthetic” mouse embryos from stem cells without a father’s sperm or a mother’s egg or uterus.
The embryos created in the lab mirror a natural mouse embryo up to 8½ days after fertilization and contain the same structures, including one resembling a beating heart.
In the near future, researchers hope to be able to use these so-called embryoids to better understand early developmental stages and study mechanisms behind diseases without requiring as many laboratory animals. The feat could also lay the groundwork for creating synthetic human embryos for future research.
“We are undoubtedly facing a new technological revolution, still very inefficient… but with huge potential,” said Lluís Montoliu, research professor at the National Biotechnology Center in Spain, who is not involved in the research. “It commemorates such spectacular scientific advances as the birth of Dolly the Sheep” and others.
A study by Magdalena Zernicka-Goetz of the California Institute of Technology and her colleagues, published Thursday in the journal Nature, was the latest to describe the synthetic mouse embryos. A similar study by Jacob Hanna of the Weizmann Institute of Science in Israel and his colleagues was published in the journal Cell earlier this month. Hanna was also a co-author of the Nature paper.
Zernicka-Goetz, an expert in stem cell biology, said one reason for studying the early stages of development is to learn more about why the majority of human pregnancies are lost at an early stage and embryos created for in vitro fertilization are created do not implant and develop in up to 70% of cases. Studying natural development is difficult for many reasons, she said, including the fact that very few human embryos are donated for research and that scientists face ethical constraints.
Building embryo models is an alternative way to study these issues.
To create the synthetic embryos, or “embryoids,” described in the Nature paper, scientists combined embryonic stem cells and two other types of stem cells — all from mice. They did this in the lab using a specific type of dish that allowed the three types of cells to come together. While the embryoids they created weren’t all perfect, Zernicka-Goetz said, the best ones were “indistinguishable” from natural mouse embryos. In addition to the heart-like structure, they also develop head-like structures.
“This is really the first model that makes it possible to study brain development in the context of the whole developing mouse embryo,” she said.
The roots of this work go back decades, and both Zernicka-Goetz and Hanna said their groups had been working on this line of research for many years. Zernicka-Goetz said her group submitted their study to Nature in November.
Scientists said the next steps include trying to get the synthetic mouse embryos to develop beyond 8½ days – with the ultimate goal of taking them to parturition, which is 20 days for a mouse.
At this point, “they are struggling to get past the 8 1/2 day mark,” said Gianluca Amadei, a co-author of the Nature paper based at the University of Cambridge. “We think that we can sort of pull them over the hill so that they can develop further.”
The scientists expect that the embryo will fail after about 11 days of development without a placenta, but they hope that one day the researchers can also find a way to create a synthetic placenta. At this point, they don’t know if they will be able to finish the synthetic embryos without a mouse uterus.
The researchers said they don’t see human versions of these synthetic embryos being created anytime soon, but do see it happening in time. Hanna called it “the next obvious thing.”
Other scientists have used human stem cells to create a “blastoid,” a structure that mimics a pre-embryo that can serve as a research alternative to a real embryo.
Such work is subject to ethical concerns. For decades, research has followed a “14-day rule” for growing human embryos in the laboratory. Last year, the International Society for Stem Cell Research recommended relaxing the rule in certain circumstances.
Scientists stress that creating a baby from a synthetic human embryo is neither possible nor contemplated.
“The perspective of this report is important because without it, the headline that a mammalian embryo was built in vitro might lead to the thought that the same thing may soon be done in humans,” said developmental biologist Alfonso Martinez Arias of the Universitat Pompeu Fabra in Spain, whose group developed alternative stem cell-based models of animal development.
“In the future, similar experiments will be done with human cells and that will eventually lead to similar results,” he said. “This should encourage reflection on the ethics and societal implications of these experiments before they take place.”
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