Scientists from institutions such as the University of Cambridge have used stem cells to grow "synthetic" embryos with brains and hearts

On August 1, scientists at the Weizmann Institute of Science in Israel published a milestone in the journal Cell in which they successfully used stem cells to grow synthetic embryonic models of mice outside the womb, a process that does not require sperm-egg binding

Natural embryos (top) and artificial embryos (bottom) show brain and heart formation side by side (Credit: Amadei and Handford)

Source: Nature

ETiX embryos reproduce the developmental milestone of native mouse embryos up to 8.
5 days (Source: Nature)

Specifically, the scientists used mouse embryonic stem cells (ESC), trophoblast stem cells (TSCs), and induced extraembryonic endoderm stem cells (iXEN) to grow stem cell-derived embryos in vitro, and this synthetic embryo reproduced the milestone
of natural mouse embryos developing in the womb to 8.
5 days.
Embryonic models show head folds with well-defined forebrain and midbrain regions and develop beating heart-like structures, including the trunk of the neural tube and solitum, tail buds containing neuromethoderm progenitor cells, intestinal tubes, and primitive germ cells
.

ETiX embryoid bodies exhibit sodroniogenesis and cardiac formation (Source: Nature)

Jianping Fu, a bioengineering expert at the University of Michigan, said: "This result is very, very exciting
.
The next milestone in this area is likely to be synthetic human embryos
based on stem cells.
”

If the methods developed by Zernica-Goetz's team prove successful on future human stem cells, they could also be used to guide the development
of synthetic organs.
"There are a lot of people around the world waiting for an organ transplant for years, and it's very exciting
that our work will most likely be used to grow synthetic human organs to save patients' lives.
" Zernicka-Goetz said
.

Share breakthrough technologies

The Zernicka-Goetz team made this breakthrough
with the help of a technique developed by Jacob Hanna, a stem cell biologist at the Weizmann Institute of Science in Israel (co-corresponding author of the Cell paper published Aug.
1).
Last year, Hanna's team reported that they had developed a device that allowed them to grow natural mouse embryos outside the womb for an unprecedented length (from 5 days to 11 days of
survival).

Last year, after Hanna's team published their paper, they shared their culture device
with other developmental and stem cell biologists.
Zernicka-Goetz and her colleagues also made slight tweaks
to the device in their experiments.

In an August 1 paper published in the journal Cell, Hanna's team described how they could use the system to allow embryos to grow for 8.
5 days
.
This is enough time for the brain region to develop, the heart to start beating, and the neural tubes and intestinal tubes to form
.

Synthetic mouse embryos grown in vials by stem cell biologist Jacob Hanna's research team (Source: Tarazi et al.
/Cell (CC BY 4.
0))

However, Hanna said the synthetic embryos look a lot like natural embryos formed by the encounter of mouse sperm and eggs, but they are "not 100% identical" and some defects and changes
in organ size can be seen.

From "mouse" to "human"

For researchers, these synthetic embryonic models have many advantages
over natural embryos created from eggs and sperm.
Because they grow outside the uterus, they are easier to observe
.
It's also easier to manipulate them
using gene-editing tools.
Therefore, the model may help reveal the role
of different genes in birth defects or developmental disorders.
Zernicka-Goetz plans to use this model to understand why
pregnancies fail.

Hanna hopes to use the technology to develop synthetic embryos for humans, providing new organs and tissues
for those in need.
But translating this research into humans won't be easy
.
Researchers have achieved the induction of human stem cells into blastocysts, and even simulated certain aspects
of embryo formation (a specific morphogenesis process during embryonic development).
However, the stage at which human cells reach organ formation occurs about a month or so after fertilization, which is a major technical challenge
.

In addition, there are ethical issues that cannot be ignored in the study of human synthetic embryos
.
The International Society for Stem Cell Research has long recommended that human embryos longer than 14 days (equivalent to 6 days in mice)
should not be cultured.
In 2021, the society lifted this restriction and issued new guidelines saying that such studies should have a compelling scientific basis and should use the minimum number of embryos
needed to achieve scientific goals.

Stem cell biologist Martin Pera argues that there is a need for ongoing discussions
about the ethics of such models.
While there hasn't been much opposition to studying human embryo models, he worries that the opposition will be even more intense
when researchers begin to develop "human embryo models that begin to develop organs.
" This opposition could jeopardize the entire field of
research.

"It's important
to conduct research in the context of some kind of ethical consensus.
" He said
.