It sounds a bit like science fiction and also a bit scary: For the first time, researchers have succeeded in creating synthetic mouse embryos that developed up to the ninth day and created organs such as the heart and brain. The team and Magdalena Zernicka-Goetz from the California Institute for Technology and the University of Cambridge used three types of stem cells instead of eggs and sperm. The results were published in the journal “Nature”.
The embryos grew in an incubator in which the physiological processes of the female rodent uterus were simulated. The researchers were able to get the stem cells to “talk” to each other, as stated in a statement. Eventually, they organized into a new biological structure and assembled into an embryo, which the researchers dubbed the “ETiX” embryo model.
In this artificial environment, the synthetic mouse embryos reached a stage that corresponds to that of natural embryos after eight to nine days, almost half the gestation period of mice, which is around 19 days. For comparison: In a human embryo, this stage of development would correspond to the first trimester of pregnancy.
During this time, the synthetic mouse embryos formed a beating heart, an intestinal tube, a neural tube, i.e. the embryonic system of the nervous system, as well as all brain regions – according to the head of the study and stem cell biologist Magdalena Zernicka-Goetz, no research team has ever succeeded in doing this.
The embryos created in the laboratory were anatomically very similar to naturally created embryos, but did not develop past the ninth day after fertilization. It is not yet understood why this blockade sets in and it would have to be overcome for further research work. Because only after that, from day 9 to 13, does organogenesis follow, in which all organs are created.
At the beginning of August, a research team led by Jacob Hanna from the Weizmann Institute in Israel published very similar results in the specialist journal Cell. They too managed to grow synthetic mouse embryos using the same artificial incubator.
According to Jesse Veenvliet, both papers would be “proof-of-principle” studies, i.e. essentially proof that it is possible to create synthetic embryos outside the womb. However, the efficiency is still very low: “In Hanna’s work, 0.1 to 0.5 percent of the embryos develop and the publication by Zernicka-Goetz does not give any precise information on this,” said the head of the “Stembryogenesis” working group. at the Max Planck Institute for Molecular Cell Biology and Genetics in Dresden opposite the Science Media Center Germany (SMC). “But one can assume that the efficiency is no more than one to two percent, possibly even less.”
Veenvliet reckons there will be a race to create the first human synthetic embryos. Transferring the findings from mice to humans is also the declared goal of Zernicka-Goetz’s team. “This will not be easy, not least because of the crucial differences in mouse and human development and in the different biology of murine and human stem cells,” says Veenvliet.
According to Michele Boiani, head of the “Mouse Embryology” working group at the Max Planck Institute for Molecular Biomedicine in Münster, it is at least technically conceivable, with the technologies used not having to last days or weeks, but months. This presents an almost insurmountable challenge, unless human development in an artificial environment is much faster than in a womb.
The synthetic embryos could in future serve as an alternative method to animal testing on early embryos. If a reproducible system for the culture of human synthetic embryos could be created, it could be investigated why some embryos do not develop further or why repeated pregnancy losses occur. Currently, observation of a mammalian embryo in detail is limited to the early stages prior to implantation of the embryo in the uterus.
If the organogenesis phase is also possible, according to Zernicka-Goetz, individual organs could be grown synthetically, which could potentially be used for organ donation. Michele Boiani suspects that such a technological development could go far: “For example, the approach that synthetic embryos reconstructed from stem cells alone could enable the reproductive cloning of humans, which so many of us feared years ago.” Commented on the issue of cloning also Lluís Montoliu, research professor at the National Center for Biotechnology in Madrid. “We are undoubtedly facing a new technological revolution, which, while still very inefficient – it is very difficult to get stem cells to spontaneously create a synthetic embryo – has enormous potential,” he said. The discovery is reminiscent of scientific advances such as the birth of the cloned sheep Dolly in 1997, which reconstructed an embryo from an egg cell and the nucleus of a body cell.
However, ethical and legal rules would stand in the way of such a scientific breakthrough. Although the International Society for Stem Cell Research (ISSCR) allows the production of human embryos, they may only grow and be examined in the laboratory up to the 14th day. Transmission into the uterus is prohibited. This rule applies in many countries around the world, including Great Britain, where the current study was carried out. In Germany, the Embryo Protection Act prohibits experiments on human embryos. Embryos may only be created with the aim of bringing about a pregnancy.
According to Jesse Veenvliet, there are still no clear rules worldwide for synthetic embryos. In the future, it is likely to increasingly depend on the extent to which they resemble human beings with the capacity to develop and should accordingly be classified as human embryos. “It will be crucial to assess this on a case-by-case basis, also in line with the international ethical framework that I believe will be developed over the next few months, with the ISSCR playing a leading role,” said Veenvliet. “One might wonder whether the ethical and legal concerns raised by the creation of similar human synthetic embryos mean that they should be addressed before attempting to create such embryos,” he said.