Scientists have created “synthetic” mouse embryos from stem cells without the father’s sperm, egg or mother’s uterus.
The lab-grown 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 short term, the researchers hope to use these so-called embryos to better understand the early stages of development and study the mechanisms behind the disease without the need for so 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 enormous potential,” said Lluís Montoliu, a research professor at the National Biotechnology Center in Spain who was not part of the research. “It’s reminiscent of spectacular scientific breakthroughs like 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 also co-authored the Nature paper.
Zernicka-Goetz, an expert in stem cell biology, said one reason to study the early stages of development is to gain more information about why most human pregnancies are lost at an early stage and embryos created for in vitro fertilization are not. can deploy 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.
The construction of embryo models is an alternative way of studying these questions.
To create the synthetic embryos, or “embryoids,” described in the Nature paper, the 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 cell types to come together. While the embryos they created weren’t all perfect, Zernicka-Goetz said, the best 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 allows us to study brain development in the context of the entire developing mouse embryo,” she said.
The roots of this work go back decades, and both Zernicka-Goetz and Hanna said their groups have been working in this line of research for many years. Zernicka-Goetz said her group presented their study to Nature in November.
The scientists said the next steps include trying to coax the synthetic mouse embryos to develop within the last 8 1/2 days — with the ultimate goal of bringing them to term, which is 20 days for a mouse.
At this point, they’re “struggling to get past” the 8.5-day mark, said Gianluca Amadei, co-author of the Nature paper at the University of Cambridge. “We think that we will be able to overcome them, so to speak, so that they can continue to develop.”
Scientists expect that after about 11 days of development, the embryo will fail without a placenta, but hope that researchers may someday find a way to create a synthetic placenta. At this point, they don’t know if they’ll be able to carry the synthetic embryos to completion without a mouse uterus.
The researchers said they don’t see the creation of human versions of these synthetic embryos anytime soon, but they do see it happening over time. Hanna called it “the next obvious thing.”
Other scientists have already used human stem cells to create a “blastoid”, a structure that mimics a pre-embryo, which could serve as a research alternative to a real one.
This work is subject to ethical concerns. For decades, a “14-day rule” about growing embryos in a lab, growing human embryos in a lab, has guided the researchers. Last year, the International Society for Stem Cell Research recommended relaxing the rule in limited circumstances.
Scientists emphasize that growing a baby from a synthetic human embryo is not possible and is not being considered.
“The perspective of this report is important, as without it, the headline that a mammalian embryo was built in vitro could lead to thinking that the same could be done with humans soon,” said developmental biologist Alfonso Martinez Arias, from the Universitat Pompeu Fabra. in Spain, whose group developed alternative models of animal development based on stem cells.
“In the future, similar experiments will be done with human cells that, at some point, will produce similar results,” he said. “This should encourage consideration of the ethics and social impact of these experiments before they take place.”
The Associated Press Department of Health and Science receives support from the Science Education Department of the Howard Hughes Medical Institute. The AP is solely responsible for all content.