Researchers in Israel have observed the formation of the placenta, yolk sac and some organs, in embryo models derived entirely from mouse embryonic stem cells.
The research was performed at the Weizmann Institute of Science in Rehovot, and was published in the journal Cell. Previous work by the team published in Nature last year had focused on developing ways to successfully grow embryos outside of the uterus, or ex utero, a process employed again for this study (see BioNews 1090). However previous work by the team had focused on growing embryos removed from a mouse uterus after two days, in the simulated uterus they developed, whereas their latest study shows embryo models made entirely from embryonic stem cells could reach the stage where organs start to form, outside of the uterus. They were also able to induce embryonic stem cells to produce cells and structures that would go on to develop into the placenta, amniotic membrane and yolk sac.
Lead researcher Professor Jacob Hanna said: 'Until now, in most studies, the specialised cells were often either hard to produce or aberrant, and they tended to form a mishmash instead of well-structured tissue suitable for transplantation. We managed to overcome these hurdles by unleashing the self-organisation potential encoded in the stem cells.'
To develop the structures, the researchers took mouse embryonic stem cells, and divided them into three groups. One group was destined to develop into embryonic organs, while the other two were treated in a way to give rise to either placental cells or the yolk sac – so-called extra-embryonic structures that are required to support the developing embryo.
All three cell types were then mixed together, and incubated in the artificial womb the team had previously developed.
Soon after being mixed together, the cells self-organised into aggregates. However, overall the experiment was highly error-prone as 99.5 percent of these aggregates failed to develop further. Nonetheless, 0.5 percent (around 50 of 10,000 aggregates) did go on to form spheres, which later changed further into elongated, embryo-like structures.
These were allowed to develop for eight and a half days, a third of the gestation of a mouse. By this point, they had formed a beating heart, blood stem cell circulation, rudimentary brain with folds, a neural tube and a gut tube.
Gene expression patterns in the embryo models were mapped and researchers found they were 95 percent similar to natural mouse models.
Dr James Briscoe, principal group leader and assistant research director, at the Francis Crick Institute, said: 'The study has broad implications as although the prospect of synthetic human embryos is still distant, it will be crucial to engage in wider discussions about the legal and ethical implications of such research.'
Sources and References
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Expert reaction to study generating a synthetic mouse embryo model from stem cells
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Post-gastrulation synthetic embryos generated ex utero from mouse naïve ESCs
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Without egg, sperm or womb: synthetic mouse embryo models created solely from stem cells
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Scientists create synthetic mouse embryos, a potential key to healing humans
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Synthetic mouse embryos created from stem cells — without sperm, eggs, or a uterus
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