The journey of life begins with a solitary fertilized cell and culminates in the creation of a complex organism comprised of innumerable specialized cells. Nonetheless, a pivotal inquiry that has long intrigued biologists has been how to unravel the mysteries surrounding the initial stages of life’s development.
In their quest to comprehend the initial weeks of existence, researchers have embraced synthetic embryo models.
How did it all start?
The Cambridge-Caltech work hasn’t been published in any scientific journals yet. Instead, Professor Magdalena Żernicka-Goetz from Cambridge and Caltech universities presented it in an address to the International Society for Stem Cell Research annual conference in Boston.
The study marks a continuation of previous attempts to generate synthetic embryos using stem cells from mice and monkeys. In earlier studies, Żernicka-Goetz’s research team and a competing group at the Weizmann Institute in Israel demonstrated that mouse stem cells could be guided to autonomously organize into structures resembling early embryos. Those featured rudimentary intestinal tracts, the initial formations of a brain, and even a pulsating heart.
Subsequently, a race ensued to extend this research to human models, and multiple teams have successfully replicated the earliest phases of human development. This groundbreaking achievement represents the first instance of successfully constructing a synthetic human embryo using human stem cells.
Motivation for the work
Currently, there is no immediate possibility of using synthetic embryos for clinical purposes. Implanting them into a patient’s womb would be against the law, and it remains uncertain whether these structures possess the capability to progress and mature beyond the initial stages of development.
Source: Little Angel IVF
The driving force behind this research is the scientists’ aspiration to unravel the mysteries behind the “black box” stage of development. This phase has earned its name because current regulations permit scientists to cultivate embryos in the laboratory for a maximum of 14 days only. Beyond this point, researchers rely on pregnancy scans and donated embryos to gain insights into the subsequent stages of development.
Derived from individual embryonic stem cells, these model structures successfully reached the initial phase of development known as gastrulation. During this stage, the embryo undergoes a transformative process where the originally contiguous cell sheet begins to differentiate into distinct cell lineages, establishing the fundamental body axes.
The idea is that if you really model normal human embryonic development using stem cells, you can gain an awful lot of information about how we begin development, what can go wrong, without having to use early embryos for research.
Although the models have not yet developed a beating heart, gut, or early brain structures at this stage, they did exhibit the presence of primordial cells that serve as precursors to egg and sperm cells.
An embryo model with beating heart cells
Another pioneering study was carried out at the Gurdon Institute at the University of Cambridge. Just days after Professor Żernicka-Goetz presented the work of her team at the conference in Boston, scientists at the Gurdon Institute have developed a synthetic human embryo model with a heartbeat and traces of blood.
Using human stem cells and bypassing the requirement for fertilization, the synthetic model successfully replicated certain cells and structures observed during the third and fourth week of pregnancy. But, unlike the Żernicka-Goetz’s model, it was intentionally engineered to lack the tissues responsible for forming the placenta and yolk sac in a natural embryo. As a result, it lacked the theoretical capacity to develop into a fetus.
The most recent model of an embryo successfully mimics some of the most advanced characteristics observed thus far. This includes the presence of beating heart cells, a milestone usually observed around day 23 in a natural embryo. The model also exhibits indications of red blood, a development that typically occurs during the fourth week of embryonic growth.
Significance of such studies
Besides offering a new method of recreating initial stages of life, these two advances may have significant application in different medical fields. To remind, such a breakthrough in development offers a unique opportunity to decipher the underlying mechanisms of different genetic disorders and gain insights into the factors contributing to recurrent miscarriages.
The artificially cultivated model could also help the pharmaceutical industry to evaluate the impact of specific medications on embryos. Additionally, it could serve as a valuable tool for exploring potential connections between gestational diabetes and cardiac abnormalities in newborns.
One thing is certain, the developments like these have only scratched the surface and there is a lot more to discover. Both breakthroughs serve as fundamental milestones, and the newfound ability to create synthetic models offers scientists a distinctive opportunity to gain valuable insights into embryonic processes that were previously challenging to observe.
Yet, certain ethical challenges and stringent regulations surrounding research on human embryos may pose obstacles to scientific investigations in this field.
The rapid progress in this field of science has brought to attention the widening gap between scientific advancements and existing regulations. Scientists in the UK and other countries are proactively taking steps to establish voluntary guidelines that will govern research on synthetic embryos, recognizing the need to address ethical and legal considerations that have emerged as a result of these developments.
If the whole intention is that these models are very much like normal embryos, then in a way they should be treated the same. Currently in legislation they’re not. People are worried about this.
Robin Lovell-Badge, Francis Crick Institute in London, for the Guardian
Another crucial question that remains unanswered is whether these structures have the capacity to develop into living organisms. In the experiment with synthetic embryos derived from mice, cells were reported to bear a striking resemblance to natural embryos. However, their implantation into female mice did not result in the development of live animals.
In April this year, scientists in China generated synthetic embryos using cells from monkeys and implanted them into the wombs of adult monkeys. While a few monkeys displayed early signs of pregnancy, none of them progressed beyond a few days of development. Researchers are uncertain whether the limitation in achieving more advanced development is solely due to technical obstacles or if it stems from underlying biological factors.