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Scientists use stem cells to create synthetic mouse embryos

Scientists have created “synthetic” mouse embryos from stem cells without the father’s sperm and the mother’s egg or womb.

The lab-created embryos mirror a natural mouse embryo up to 8 ½ 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 embryoids to better understand early stages of development and study the mechanisms behind disease without the need for so many lab animals. The feat could also lay the groundwork for creating synthetic human embryos for future research.

“Without a doubt we are facing a new technological revolution, still very inefficient… but with enormous potential,” said Lluís Montoliu, a research professor at Spain’s National Center for Biotechnology who is not part of the research. “Remember scientific breakthroughs as spectacular as the birth of Dolly the sheep” and others.

This microscope image shows a synthetic mouse embryo with colors added to show the formation of the brain and heart.Gianluca Amadei, Charlotte Handford via AP

A study published Thursday in the nature magazine, by Magdalena Zernicka-Goetz at the California Institute of Technology and colleagues, the latest to describe synthetic mouse embryos. A similar study, conducted 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 a co-author of the Nature article.

Zernicka-Goetz, an expert in stem cell biology, said one reason for studying the earliest stages of development is to better understand why most human pregnancies are lost at an early stage and embryos created for in vitro fertilization they are not implanted 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 restrictions.

Embryo model building is an alternative way to study these issues.

To create the synthetic embryos, or “embryoids,” 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 particular 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. In addition to the heart-shaped structure, they also develop head-shaped structures.

This combination of microscope images shows natural, superior, and synthetic mouse embryos with colors added to show comparable brain and heart formation.
This combination of microscope images shows natural, superior, and synthetic mouse embryos with colors added to show comparable brain and heart formation.Gianluca Amadei, Charlotte Handford via AP

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

The roots of this work go back decades, and both Zernicka-Goetz and Hanna said their groups worked on this line of research for many years. Zernicka-Goetz said her group submitted her study to Nature in November.

The scientists said next steps include trying to coax synthetic mouse embryos to develop beyond 8 1/2 days, with the ultimate goal of bringing them to term, which is 20 days for a mouse.

At this point, they “struggle to get past” the 8 1/2-day mark, said Gianluca Amadei, a co-author of the Nature paper based at the University of Cambridge. “We believe that we will be able to overcome them, so to speak, so that they can continue to develop.”

Scientists hope that after about 11 days of development, the embryo will fail without a placenta, but hope that one day researchers may also 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 human versions of these synthetic embryos being created any time soon, but they do see it happening in time. Hanna called it “the next obvious thing.”

Image: Dr. Jacob Hanna, a molecular geneticist at the Weizmann Institute of Sciences in Israel, holds a vial containing five-day-old synthetic mouse embryos grown on an electronically controlled ex-utero roller culture platform, in a laboratory in Rehovot, Israel.  on August 4, 2022.
dr Jacob Hanna, a molecular geneticist at the Weizmann Institute of Sciences in Israel, holds up a vial containing five-day-old synthetic mouse embryos grown on an electronically controlled ex-utero roller culture platform in a laboratory in Rehovot, Israel, on August 4. .Ahmad Gharabli / AFP – Getty Images Archive

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 concerns. For decades, a “14-day rule” for 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 stress that raising a baby from a synthetic human embryo is neither possible nor under consideration.

“The perspective of this report is important since, without it, the headline that a mammalian embryo has been built in vitro may lead one to think that the same thing will soon be able to be done with humans,” said developmental biologist Alfonso Martínez. Arias, from the 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 that will, at some point, yield similar results,” he said. “This should encourage considerations about the ethics and social impact of these experiments before they happen.”

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