Mouse embryos grown without eggs or sperm: why and what’s next?

Amazing stuff! This is huge!

I have speculated here several times before that probably in about 20-30 years from now women will not have to give birth anymore unless they choose otherwise. In the not so distant future, new human life can be born ex utero and God will be smiling.

"Under the right conditions, stem cells can divide and self-organize into an embryo on their own. In studies published in Cell and Nature this month, two groups report that they have grown synthetic mouse embryos for longer than ever before. The embryos grew for 8.5 days, long enough for them to develop distinct organs — a beating heart, a gut tube and even neural folds.
The process is far from perfect. Just a tiny fraction of the cells develop these features and those that do don’t entirely mimic a natural embryo. But the work still represents a major advance that will help scientists to see organ development in unprecedented detail. ...
The two research teams achieved the feat using similar techniques. ... has been working on this problem for a decade. “We started with only embryonic stem cells,” ... “They can mimic early stages of development, but we couldn’t take it any further.” Then, a few years ago, her team discovered that when they added stem cells that give rise to the placenta and yolk sac, their embryos developed further. Last year, they demonstrated that they could use this technique to culture embryos until day 7. ...
team also conducted an experiment in which they knocked out a gene called Pax6, which has a key role in brain development. When they eliminated this gene, the mouse heads didn’t develop correctly, mimicking what occurs in natural embryos that lack that gene. The result demonstrates “that the system is actually functional” ...
For researchers, these synthetic models have many advantages over natural embryos created from eggs and sperm. Because they grow outside of the uterus, they’re much easier to observe. They’re also easier to manipulate using genome-editing tools. ..."

From the first abstract:

"In vitro cultured stem cells with distinct developmental capacities can contribute to embryonic or extraembryonic tissues after microinjection into pre-implantation mammalian embryos. However, whether cultured stem cells can independently give rise to entire gastrulating embryo-like structures with embryonic and extraembryonic compartments remains unknown. Here, we adapt a recently established platform for prolonged ex utero growth of natural embryos to generate mouse post-gastrulation synthetic whole embryo models (sEmbryos), with both embryonic and extraembryonic compartments, starting solely from naive ESCs. This was achieved by co-aggregating non-transduced ESCs, with naive ESCs transiently expressing Cdx2 or Gata4 to promote their priming toward trophectoderm and primitive endoderm lineages, respectively. sEmbryos adequately accomplish gastrulation, advance through key developmental milestones, and develop organ progenitors within complex extraembryonic compartments similar to E8.5 stage mouse embryos. Our findings highlight the plastic potential of naive pluripotent cells to self-organize and functionally reconstitute and model the entire mammalian embryo beyond gastrulation."

From the second abstract:

"Embryonic stem cells (ESC) can undergo many aspects of mammalian embryogenesis in vitro, but their developmental potential is substantially extended by interactions with extraembryonic stem cells, including trophoblast stem cells (TSCs), extraembryonic endoderm stem cells (XEN), and inducible-XEN cells (iXEN). Here, we assembled stem-cell derived embryos in vitro from mouse ESCs, TSCs and iXEN cells and showed that they recapitulate whole natural mouse embryo development in utero to day 8.5. Our embryo model displays head-folds with defined forebrain and midbrain regions and develops a beating heart-like structure, a trunk comprising a neural tube and somites, a tail bud containing neuromesodermal progenitors, a gut tube, and primordial germ cells. This complete embryo model develops within an extra-embryonic yolk sac that initiates blood island development. Importantly, we demonstrate that the neurulating embryo model assembled from Pax6 knockout-ESCs aggregated with wild-type TSCs and iXENs recapitulates the ventral domain expansion of the neural tube that occurs in natural, ubiquitous Pax6 knockout embryos. Thus, these complete embryoids are a powerful in vitro model for dissecting the roles of diverse lineages and genes in development. Our results demonstrate the self-organization ability of embryonic and two types of extra-embryonic stem cells to reconstitute mammalian development through and beyond gastrulation to neurulation and early organogenesis."

Mouse embryos grown without eggs or sperm: why and what’s next? Two research teams grew synthetic embryos using stem cells, long enough to see some organs develop.

Post-gastrulation synthetic embryos generated ex utero from mouse naive ESCs (open access)

Synthetic embryos complete gastrulation to neurulation and organogenesis (no public access)