Scientists use stem cells to create synthetic mouse embryos

Scientists have created “synthetic” mouse embryos from either the father’s sperm or the mother’s egg or stem cells from the uterus.

The lab-created embryos resemble natural mouse embryos up to 8.5 days after fertilization and contain the same structures, including those like a beating heart.

In the short term, researchers hope to use these so-called embryoid bodies to better understand early developmental stages and study the mechanisms behind disease without requiring as many laboratory animals as possible. The feat could also lay the groundwork for future research to create synthetic human embryos.

“We are undoubtedly facing a new technological revolution, although the efficiency is still low…but the potential is huge,” said Lluís Montoliu, a research professor at Spain’s National Center for Biotechnology, who was not involved in the study. “This is reminiscent of amazing scientific advances like the birth of Dolly the Sheep” et al.

A study published Thursday in the journal NatureWritten by Caltech’s Magdalena Zernicka-Goetz and her colleagues, is the latest to describe synthetic mouse embryos. Earlier this month, Jacob Hanna and colleagues at the Weizmann Institute of Science in Israel conducted a similar study. In the journal Cell. Hanna is also a co-author of the Nature paper.

Stem cell biology expert Zernicka-Goetz says one reason to study early developmental stages is to gain a deeper understanding of why most human pregnancies fail at an early stage, while embryos created for in vitro fertilization fail to implant and up to 70 percent of the time case occurred. Studying natural development is difficult for a number of reasons, including few human embryos donated for research and scientists facing ethical constraints, she said.

Building embryo models is another way to study these questions.

To create synthetic embryos, or “embryo-like,” the scientists combined embryonic stem cells with two other types of stem cells — all derived from mice. They did this in the lab, using a special type of petri dish that brought the three types of cells together. Zernicka-Goetz said that while the embryoids they created were not perfect, the best ones were “indistinguishable” from natural mouse embryos. In addition to the heart-shaped structure, they also developed a head-shaped structure.

“This is really the first model that allows you to study brain development in the context of the entire developing mouse embryo,” she said.

The roots of the work go back decades, and both Zernicka-Goetz and Hanna say their teams have been working in this direction for years. Zernicka-Goetz said her team submitted the study to Nature in November.

The next steps, the scientists say, include trying to coax synthetic mouse embryos to develop beyond 8.5 days—the ultimate goal is to bring them to term, which in mice is 20 days.

At this point, they were “trying to beat” the 8 1/2-day mark, said Gianluca Amadei, co-author of the Nature paper at the University of Cambridge. “We think we’re going to be able to get them through, so to speak, so they can continue to develop.”

Scientists expect embryos to fail after about 11 days of development without a placenta, but they hope researchers will also one day find a way to create a synthetic placenta. At this point, they didn’t know if they could always obtain synthetic embryos without the mouse uterus.

The researchers say they won’t see human versions of these synthetic embryos anytime soon, but it does happen in time. Hannah called it “the next obvious thing.”

Other scientists have used human stem cells to create an “embryo-like cell, “A structure that mimics a pre-embryo and can be studied as a surrogate for a real embryo.

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

Scientists stress that growing babies from synthetic human embryos is neither possible nor under consideration.

Alfonso Martinez Arias, a developmental biologist at the University of Pompeu Fabra, said: “The perception of this report is important because without it mammalian embryos have been constructed in vitro for the title of may lead to the belief that the same study could soon be done in humans.” In Spain, the group has developed an alternative animal developmental model based on stem cells.

“In the future, similar experiments will be performed on human cells and will at some point yield similar results,” he said. “This should encourage consideration of the ethical and social implications of these experiments before they take place.”

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

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