Scientists have created “synthetic” mouse embryos from stem cells without the father’s sperm or the mother’s egg or embryo.
The lab-created embryos mimic natural mouse embryos up to 8 ½ days after fertilization, including structures such as a beating heart.
In the near term, researchers hope to use these so-called embryos to better understand the early stages of development and study the mechanisms behind disease without the need for more laboratory animals. This feat could also lay the foundation for creating artificial human embryos for research in the future.
“We are undoubtedly facing a new technological revolution, still very inefficient … but with huge potential,” said researcher Professor Luis Montolue of the National Biotechnology Center in Spain, who was not part of the research. “It is reminiscent of spectacular scientific advances like the birth of Dolly the sheep” and others.
The study, published Thursday in the journal Nature by Magdalena Zernica-Goetz at the California Institute of Technology and her colleagues, was the latest to describe artificial mouse embryos. A similar study by Jacob Hanna and his colleagues at the Weizmann Institute of Science in Israel was published earlier this month in the journal Cell. Hannah was also a coauthor on the Nature paper.
Zernicka-Goetz, an expert in stem cell biology, said one reason to study the early stages of development is to learn more about why most human pregnancies are lost early and why embryos prepared for in vitro fertilization fail to implant. develops in 70% of cases. Studying natural development is difficult for several reasons, she said, including that very few human embryos are donated for research and that scientists face ethical constraints.
An alternative way to study these problems is to create embryonic models.
To create the artificial 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 special type of dish that allowed the three types of cells to coexist. Although not all of the embryos they created were perfect, Zernicka-Goetz said, the best embryos were “indistinguishable” from natural mouse embryos. Apart from the heart-like structure, they also develop a head-like 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 this work go back decades, and both Zernicka-Goetz and Hanna said their groups have been working on this research for years. Zernicka-Goetz said her group submitted their study to Nature in November.
The scientists said the next steps would include trying to incubate artificial mouse embryos for 8 ½ days to develop — with the ultimate goal of reaching that, which is 20 days for a mouse.
At this point, they “struggle to get past” the 8 1/2-day mark, said Gianluca Amadei, coauthor of the Nature paper at the University of Cambridge. “We think we’ll be able to get them over the hump, so to speak, so they can develop.”
Scientists expect that a fetus will fail without a placenta after about 11 days of development, but they hope that researchers will someday be able to find a way to create an artificial placenta as well. At this point, they don’t know if they can get artificial embryos entirely without mouse embryos.
The researchers said they don’t see creating human versions of these artificial 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 that mimics a pre-embryo, which could actually serve as a research option.
Such work is subject to ethical concerns. For decades, the “14-day rule” has guided researchers on growing human embryos in the laboratory. Last year, the International Society for Stem Cell Research recommended relaxing the rules in limited circumstances.
Scientists stress that growing a baby from an artificial human embryo is neither possible nor under consideration.
“The approach to this report is important because, besides, mammalian embryos have been created in vitro, the headline may lead to the thought that the same can be done with humans soon,” said Alfonso Martínez Arias, a developmental biologist at the Universitat Pompeu Fabra. in Spain, whose group has developed alternative stem cell-based models of animal development.
“In the future, similar experiments will be performed on human cells and at some point similar results will be obtained,” he said. “It should encourage consideration of the ethics and social impact of these experiments before they take place.”