Scientists have created “synthetic” mouse embryos from stem cells without the father’s sperm or the mother’s egg or uterus.
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 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.
“Without a doubt, we are facing a new technological revolution, still very inefficient, but with enormous potential”, explains Lluis Montoliu, a research professor at Spain’s National Biotechnology Center who is not part of the research. “Remember 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 of the California Institute of Technology and her colleagues, was the latest to describe the synthetic mouse embryos. A similar study, by Jacob Hanna of Israel’s Weizmann Institute of Science and 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 for studying the early stages of development is to learn more about why most human pregnancies are lost at an early stage and embryos created by in IVF they do not implant and do not implant. develop 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.
Building model embryos is an alternative way of studying these problems.
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 particular type of dish that allowed the three types of cells to stick together. Although the embryoids they created weren’t 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 groups had been working on this line of research for many years. Zernicka-Goetz said her group presented their study in Nature in November.
The scientists said the next steps include trying to coax the synthetic mouse embryos to develop past 8 1/2 days, with the ultimate goal of bringing them to term, 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 Nature paper co-author based at the University of Cambridge. “We think we can get them over the hump, 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 can one day also find a way to create a synthetic placenta. At this point, they don’t know if they can get the synthetic embryos to term without the mouse uterus.
The researchers said they don’t see creating human versions of these synthetic embryos anytime soon, but they do see it in 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 can serve as a research alternative to a real one.
This work is subject to ethical concerns. For decades, a “14-day rule” on the growth of embryos in the laboratory the growth of 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 being considered.
“The perspective of this report is important because, without it, the headline that a mammalian embryo has been built in vitro may suggest that the same can soon be done in humans,” said developmental biologist Alfonso Martinez Arias from Pompeu Fabra University. in Spain, whose group has developed alternative models of animal development based on stem cells.
“In the future, similar experiments will be done with human cells and will, at some point, give similar results,” he said. “This should encourage considerations about the ethics and social impact of such experiments before they occur.”
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