Researchers have created “complete” models of human embryos from stem cells in the lab and grown them outside the womb, in work that paves the way for advances in fertility, pharmaceutical testing and transplants.
The tiny balls of tissue were made by combining stem cells that arranged themselves into structures that mimic the 3D organisation of all the known features found in human embryos from one to two weeks old.
“This is the first embryo model that has structural compartment organisation and morphological similarity to a human embryo at day 14,” said Prof Jacob Hanna, who led the research at the Weizmann Institute in Israel. At two weeks, the balls of cells were about half a millimetre wide.
The field has produced a flurry of papers in recent months from scientists who have combined stem cells to create human embryo-like structures without the need for eggs or sperm.
While the minuscule structures are not identical to human embryos, researchers hope they will soon be good enough to help shed light on the mysteries of the earliest stages of human development and so far unknown causes of miscarriage.
Understanding embryo development – particularly from two weeks in the womb – is only one area where scientists see model embryos having an impact. Another scenario Hanna envisages is the creation of model embryos from the skin cells of ill patients. Grow the model embryos for a month or so and they will start to develop organs that can be used as a source of cells to transplant into the patients, he says.
“Do they have the right to give their own skin cells to make an embryo model and make cells that will save their lives or solve their medical need? That is the scenario that should be considered,” Hanna told the Guardian. Before growing a model embryo for donor tissue, scientists would tweak its genetics to ensure it did not develop a brain or nervous system, he added.
Another application scientists have in mind is using model embryos to assess the probable impact of medicines on real human embryos. Since pregnant women are often excluded from clinical trials, doctors are in the dark about the side-effects of even some of the most common treatments on pregnant women and babies.
Writing in Nature, the scientists describe how they built on procedures from last year to create model mouse embryos. They mixed together “naive” human stem cells, which are capable of turning into different cell types, and found that about 1% arranged themselves into “complete” embryo-like structures. These went on to develop a placenta, a yolk sac, an outer membrane called the chorionic sac and other features expected in human embryos of the same age.
The freshly made model embryos are equivalent to week-old human embryos and are cultured in the lab for a further week. Because of their age at creation, Hanna said it was “biologically impossible” for them to implant into a womb. “This cannot be used for pregnancy,” he said.
Nevertheless, the scientists used a pregnancy test to assess how well the model embryos were growing; when fluid from the dish was put on a test strip, it returned a positive result.
Dr Peter Rugg-Gunn, who studies embryonic development at the Babraham Institute near Cambridge, said the work was “impressive” and “significant”, but noted that not all the features of early human embryos were perfectly replicated. For example, the trophoblast, a precursor of the placenta, was present but not properly organised.
“This embryo model would not be able to develop if transferred into a womb, because it bypasses the stage needed to attach to the womb lining,” Rugg-Gunn said.
But he said the work, and similar studies, “do raise important ethical considerations”. “Thorough evaluation and discussions on this important subject are under way internationally and in the UK through the Governance of Stem Cell-Based Embryo Models project,” he said.
