Researchers have followed a “14-day rule” for generating human embryos in the lab for many years. The International Society for Stem Cell Research suggested modifying the regulation in specific instances last year. Now, scientists have managed to create mouse embryos without sperm or eggs.
Without a mother’s egg or womb or a father’s sperm, scientists have developed “synthetic” mouse embryos from stem cells.
The lab-created embryos resemble a real mouse embryo up to 8 ½ weeks after fertilization, with the identical features, including one like a beating heart.
In the near future, scientists want to be able to investigate disease causes and early stages of development without using as many lab animals by using these so-called embryoids. The accomplishment could serve as a springboard for later attempts to produce artificial human embryos for research.
“We are undoubtedly facing a new technological revolution, still very inefficient … but with enormous potential,” said Lluís Montoliu, a research professor at the National Biotechnology Centre 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.
Magdalena Zernicka-Goetz from the California Institute of Technology and her colleagues’ paper, which was published Thursday in the journal Nature, is the most recent to detail the synthetic mouse embryos. Jacob Hanna from the Weizmann Institute of Science in Israel and his coworkers published a related study (read below) earlier this month in the journal Cell. Hanna contributed to the study in Nature as a coauthor as well.
According to Zernicka-Goetz, a stem cell biology expert, one motivation to investigate the early phases of development is to have a better understanding of why the majority of human pregnancies end prematurely and embryos generated for in vitro fertilization fail to implant and develop in up to 70% of cases. Natural development research is challenging for a variety of reasons, she explained, including the fact that only a few human embryos are contributed for study and researchers face ethical restraints.
Creating embryo models is an alternative method of investigating these challenges.
Scientists combined embryonic stem cells with two other types of stem cells derived from mice to construct the synthetic embryos, or “embryoids” mentioned in the Nature publication. They performed this in the lab, using a special dish that allowed the three types of cells to mix. While not all of the embryoids they made were excellent, Zernicka-Goetz stated that the best ones were “indistinguishable” from real mouse embryos. They grow head-like structures in addition to the heart-like structure.
”This is really the first model that allows you to study brain development in the context of the whole developing mouse embryo,” she said.
This work has decades of origins, and both Zernicka-Goetz and Hanna stated that their groups have been concentrating on this field of research for a long time. Zernicka-Goetz stated that her research was submitted to Nature in November.
The next stage, according to the researchers, is to try to coax the synthetic mouse embryos to develop past 8 ½ days, with the ultimate objective of getting them to term, which is 20 days for a mouse.
They currently “struggle to go past” the 8 ½-day barrier, according to Gianluca Amadei, a University of Cambridge researcher and coauthor on the Nature research. “We think that we will be able to get them over the hump, so to speak, so they can continue developing.”
The scientists believe that without a placenta, the embryo will perish after around 11 days of development, but they hope that researchers will eventually discover a technique to make a synthetic placenta. They do not know if they will be able to carry the synthetic embryos to term without a mouse womb at this moment.
Researchers said they do not expect to see human equivalents of these synthetic embryos anytime soon, but they believe it will happen eventually. Hanna referred to it as “the next obvious thing.”
Other researchers have already employed human stem cells to produce a “blastoid,” a structure that resembles a pre-embryo that can be used as a study alternative to a genuine one.
Such work raises ethical questions. Researchers have followed a “14-day rule” for generating human embryos in the lab for many years. The International Society for Stem Cell Research suggested modifying the regulation in specific instances last year.
Scientists emphasize that it is neither feasible nor being considered to create a human offspring from a synthetic embryo.
“Perspective on this report is important since, without it, the headline that a mammalian embryo has been built in vitro can lead to the thought that the same can be done with humans soon,” remarked Alfonso Martinez Arias of the Universitat Pompeu Fabra in Spain, whose lab has produced alternative stem cell-based animal development models.
“In the future, similar experiments will be done with human cells and that, at some point, will yield similar results,” he said. “This should encourage considerations of the ethics and societal impact of these experiments before they happen.”
Read the study below: