Scientists at the Weizmann Institute in Israel discovered that stem cells from mice could be engineered to self-assemble into early embryo-like structures with an intestinal tube, the beginnings of a brain and a beating heart. Known as synthetic embryos because they are created without fertilized eggs, the living structures are expected, in the short term, to lead to a deeper understanding of how organs and tissues form during the development of natural embryos. But the researchers believe the work could also reduce animal testing and ultimately pave the way for new sources of cells and tissues for human transplantation. For example, skin cells from a leukemia patient could potentially be turned into bone marrow stem cells to treat their condition. “Remarkably, we show that embryonic stem cells create whole synthetic embryos, meaning it includes the placenta and the yolk sac that surrounds the embryo,” said Professor Jacob Hanna, who led the effort. “We’re really excited about this work and its implications.” The work is published in Cell. Last year, the same team described how they had constructed an engineered womb that allowed natural mouse embryos to grow outside the womb for several days. In the most recent work, the same device was used to grow mouse stem cells for more than a week, almost half the gestation time for a mouse. Some of the cells were pretreated with chemicals that activated genetic programs to develop into a placenta or yolk sac, while others grew without intervention into organs and other tissues. While most of the stem cells failed to form embryo-like structures, about 0.5% coalesced into small balls that developed into different tissues and organs. Compared to natural mouse embryos, the synthetic embryos were 95% identical in terms of their internal structure and genetic cell profiles. As far as the scientists could tell, the organs that formed were functional. Hanna said the synthetic embryos weren’t “real” embryos and didn’t have the potential to develop into living animals, or at least they didn’t when they were transplanted into the wombs of female mice. He has founded a company called Renewal Bio that aims to develop human synthetic embryos to provide tissues and cells for medical conditions. “In Israel and many other countries, such as the US and the UK, it is legal and we have ethical approval to do this with human induced pluripotent stem cells. This provides an ethical and technical alternative to using embryos,” Hanna said. Dr James Briscoe, head of the team at the Francis Crick Institute in London, who was not involved in the research, said it was important to discuss how best to set up the work before developing human synthetic embryos. “Synthetic human embryos are not an immediate prospect. We know less about human embryos than mouse embryos, and the ineffectiveness of synthetic mouse embryos suggests that translation of the findings to humans requires further development,” Briscoe said. However, he added: “Now is the right time to consider the best legal and ethical framework to regulate the research and use of human synthetic embryos and to update existing regulations.” Speaking to StatNews, Professor Paul Tesar, a geneticist at Case Western Reserve University, said that as more scientists push embryos derived from stem cells further along the development path, the more synthetic and natural embryos begin to merge. “There will always be a gray area,” he said. “But as scientists and as a society we have to come together to decide where the line is and determine what is ethically acceptable.” The creation of “synthetic” human embryos is outside the legal framework of the UK’s Human Fertilization and Embryology Act, but it would be illegal to use them to establish a pregnancy in a woman because they are not classed as “permitted embryos”.
