Scientists use stem cells to create synthetic mouse embryos

The scientists created “synthetic” mouse embryos from stem cells without the father’s sperm or the mother’s egg or uterus.

Lab-created embryos mirror a natural mouse embryo up to 8.5 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 disease without the need for as many laboratory animals. This 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, professor-researcher at the National Biotechnology Center in Spain who is not part of the research. “It is reminiscent of such spectacular scientific advances as the birth of Dolly the sheep” and others.

A study published Thursday in the Nature magazine, by Magdalena Zernicka-Goetz of the California Institute of Technology and her colleagues, was the last 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 co-author of the Nature article.

Zernicka-Goetz, an expert in stem cell biology, said one of the reasons for studying the early stages of development is to better understand why the majority of human pregnancies are lost at an early stage and the embryos created for in vitro fertilization 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.

The construction of embryo models is an alternative way to study these questions.

To create the synthetic embryos, or “embroids,” described in the Nature article, the 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 all 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. Apart from the heart-shaped structure, they also develop head-shaped structures.

“It’s 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 submitted their study to Nature in November.

The scientists said the next steps are to try to get the synthetic mouse embryos to develop beyond 8.5 days – with the ultimate goal of bringing them to full term, which is 20 days for a mouse.

At this point, they are “struggling to get past” the 8.5-day mark, said Gianluca Amadei, co-author of the Nature paper based at the University of Cambridge. “We think we can turn them around, 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 researchers can one day 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 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. Hanna called it “the next obvious thing”.

Other scientists have already used human stem cells to create a “blastoid, » a structure mimicking a pre-embryo, which can serve as a research alternative to a real one.

Such work is subject to ethical concerns. For decades, a “14-day rule” about growing human embryos in the lab has guided researchers. Last year, the International Society for Stem Cell Research recommended relaxing the rule in limited circumstances.

Scientists point out that growing a baby from a synthetic human embryo is neither possible nor envisioned.

“The perspective on this report is important because, without it, the headline that a mammalian embryo was constructed in vitro may suggest that the same may soon be done with humans,” said developmental biologist Alfonso Martinez. Arias from the Universitat Pompeu Fabra. in Spain, whose group has developed alternative models of animal development based on stem cells.

“In the future, similar experiments will be conducted with human cells and this, at some point, will yield similar results,” he said. “This should encourage reflections on the ethical and societal impact of these experiences before they happen.”

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The Associated Press Health and Science Department is supported by the Howard Hughes Medical Institute Department of Science Education. The AP is solely responsible for all content.

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