Scientists have created “synthetic” mouse embryos from stem cells without the father’s sperm or the mother’s egg or womb.
The lab-created embryos mirror a natural mouse embryo up to 8 1/2 days after fertilization, containing the same structures, including one like a beating heart.
In the near term, researchers hope to use these so-called embryoids to better understand the early stages of development and study the mechanisms behind disease without the need for so many laboratory animals. This could also lay the groundwork for creating synthetic human embryos for future research.
“We are definitely facing a new technological revolution, still very inefficient … but with great potential,” said Lluís Montoliu, a research professor at Spain’s National Biotechnology Center, who is not part of the research. “It is reminiscent of such spectacular scientific breakthroughs as the birth of Dolly the sheep” and others.
A study published Thursday in the journal Nature, by Magdalena Zernicka-Goetz at the California Institute of Technology and her colleagues, was the latest to describe synthetic mouse embryos. A similar study, by Jacob Hanna at the Weizmann Institute of Science in Israel and his colleagues, was published earlier this month in the journal Cell. Hanna was also a co-author in the journal Nature.
Zernicka-Goetz, an expert in stem cell biology, said one reason to study the early stages of development is to gain more insight into why most human pregnancies are lost at an early stage and embryos created for fertilization in vitro fail to 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 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 special 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 structure, they also develop head-like structures.
“This is really the first model that allows you to study brain development in the context of the whole developing mouse embryo,” she said.
The roots of this work go back decades, and Zernicka-Goetz and Hanna said their groups have been working on this line of research for many years. Zernicka-Goetz said her group presented its study in Nature in November.
The scientists said the next steps include trying to induce the synthetic mouse embryos to develop in 8 1/2 days – with the ultimate goal of carrying them to term, which is 20 days for a mouse.
At this point, they “try to push past” the 8 1/2-day limit, said Gianluca Amadei, a Cambridge University-based co-author on the journal Nature. “We think we’ll be able to get through them, so to speak, so they can continue to develop.”
Scientists expect that after about 11 days of development the embryo will fail without a placenta, but they hope that researchers may one day also find a way to create a synthetic placenta. At this point, they don’t know if they’ll be able to get the synthetic embryos all the way without the mouse’s stomach.
The researchers said they don’t see creating human versions of these synthetic embryos anytime soon, but they do see it happening in time. Hanna called it “the obvious next thing.”
Other scientists have already used human stem cells to create a “blastoid,” a structure that mimics a pre-embryo, that could serve as a research alternative to a real one.
Such work is subject to ethical concerns. For decades, a “14-day rule” for growing human embryos in the laboratory has guided researchers. Last year, the International Society for Stem Cell Research recommended relaxing the rule in limited circumstances.
Scientists stress that growing a baby from a synthetic human embryo is neither possible nor under consideration.
“The prospect of this report is important because, without it, the headline that a mammalian embryo has been constructed in vitro could lead to the thought that the same could be done with humans soon,” said developmental biologist Alfonso Martinez Arias of the Universitat Pompeu Fabra. . in Spain, whose group has developed alternative animal development models based on stem cells.
“In the future, similar experiments will be done with human cells that, at some point, will give similar results,” he said. “This should encourage consideration of the ethics and social impact of these experiments before they take place.”