Scientists created “synthetic” mouse embryos from stem cells without dad’s sperm or mom’s egg or uterus.
The lab-created embryos mirror a natural mouse embryo up to 8 ½ days after fertilization, containing the same structures, including a beating heart.
In the short term, researchers hope to use these so-called embryoids to better understand the early stages of development and study the mechanisms behind diseases without the need for so many laboratory animals. The feat could also lay the groundwork for creating synthetic human embryos for research in the future.
“We are undoubtedly facing a new technological revolution, very inefficient … but with enormous potential,” said Lluís Montoliu, a research professor at the National Center for Biotechnology in Spain, who is not involved in the research. “Reminiscent of such spectacular scientific advances 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 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 the majority of human pregnancies are lost early and embryos created for IVF fail to implant. and develop in up to 70% of cases. Studying natural development is difficult for many reasons, he said, including the fact that very few human embryos are donated for research and scientists face ethical constraints.
The construction of model embryos is an alternative way of studying these issues.
To create the synthetic embryos, or “embryos,” 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 kind of dish that allowed the three types of cells to come together. Although the embryos 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 allows you to study brain development in the context of the whole developing mouse embryo,” he said.
The roots of this work go back decades, and both Zernicka-Goetz and Hanna said their teams have been working on this line of research for many years. Zernicka-Goetz said her team submitted their study to Nature in November.
The scientists said the next steps include trying to get the synthetic mouse embryos to develop past 8 ½ days — with the ultimate goal of finishing, 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 on the Nature paper based at the University of Cambridge. “We think we’ll be able to ride them out, so to speak, so they can continue to grow.”
Scientists expect that after about 11 days of development the fetus will fail without a placenta, but they hope that researchers can someday also find a way to create a synthetic placenta. At this point, they don’t know if they’ll be able to take the synthetic embryos to term 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 in time. Hannah 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 can serve as a research alternative to a real one.
Such work is subject to ethical considerations. For decades, a “14-day rule” for developing human embryos in the laboratory guided researchers. Last year, the International Society for Stem Cell Research recommended relaxing the rule under 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 since, without it, the headline that a mammalian embryo has been created in vitro may lead to the thought that the same can be done with humans soon,” said developmental biologist Alfonso Martinez Arias of the Universitat Pompeu Fabra. in Spain, whose team has developed alternative animal development models based on stem cells.
“In the future, similar experiments will be done with human cells and this, at some point, will give similar results,” he said. “This should encourage consideration of the ethics and social impact of these experiments before they are done.”
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