Synthetic Embryos: The Next Frontier in Studying Development
How scientists have created synthetic embryos from stem cells — no sperm cells, egg cells, or womb needed
Advancements in stem cell science have long led to transformations in the field of biology as a whole, and great improvements in human health.
Thanks to stem cells, there are groundbreaking treatments being tested and developed for a range of diseases and health issues like diabetes, Parkinson’s disease, burns, and much more.
But recently, in August 2022, an even more mind-blowing (and somewhat ethically challenging) stem cell advancement occurred — stem cells were used to create synthetic mouse embryos in the lab until 8.5 days after fertilization. The crazy part? Scientists didn’t need to use egg cells, or sperm cells, and an artificial environment was used rather than a womb.
A Semi-Deep Dive into Stem Cells
One… Two… Three Different Types
Before we delve deeper into this discovery, how it works, and the ethical dilemmas surrounding it, we first need to ask: what are stem cells?
There are a few different types of stem cells. The stem cells present at the very beginning of development are totipotent stem cells. Think of these like babies — babies have an infinite number of career paths they can choose from and they haven’t eliminated any of those paths yet. Similarly, these stem cells can specialize into any cell type, like placental cells, and cells that form organs.
If you’re an etymology nerd, it may also help to know that totipotent comes from the Latin “totus,” meaning “whole” as these stem cells can turn into any of the cells in our whole bodies.
As embryonic development progresses, totipotent stem cells specialize further, with some of them specializing into pluripotent stem cells. These stem cells are like slightly older children; maybe, they’ve learned that they don’t enjoy math so math-related careers are out of the picture.
Of course, cells don’t have brains, so instead of making conscious decisions, their environments largely dictate the cell types they can or can’t become. More scientifically put, pluripotent stem cells can turn into any body cells like blood cells and skin cells.
Etymology-wise, “pluri,” means several so these cells can turn into several cell types but not all (specifically not cells outside of the embryo like placental cells).
By the time children are born, there are no totipotent or pluripotent stem cells remaining in their bodies. Instead, both children and adults have multipotent stem cells, the most limited of the bunch.
These cells are like teenagers or young adults, having narrowed down their career options even further. At this point, they know the general field they want to go into but not the specifics.
Examples of multipotent stem cells include blood stem cells which can specialize into red blood cells, white blood cells, and platelets.
Stem Cells & The Embryo
So how does all of this apply to the embryo? We already know that totipotent stem cells are only available at the very early stages of development (only until a few days after fertilization).
After this, we reach a stage in development called a blastocyst. This blastocyst has two main, distinct cell types. The inner cell mass which — surprise, surprise — is in the inner portion of the blastocyst, and the outer cells are called the trophectoderm. The trophectoderm gives rise to trophoblast stem cells which are multipotent.
At this point, we are at embryonic day 3.25 for a mouse embryo — this means it has been 3.25 days since fertilization.
A bit later in the blastocyst stage, at embryonic day 4.5, the inner cell mass further specializes into the epiblast and the primitive endoderm. The epiblast goes on to form every cell in the mouse’s body (with the process being similar for humans). These epiblast cells are pluripotent.
The primitive endoderm gives rise to extra-embryonic cells like parts of the yolk sac which is crucial to development but isn’t part of the body after birth.
Another important thing to note is that there are subcategories within the different stem cell types. For instance, pluripotent stem cells can be categorized into naive and primed. Naive cells have the characteristics of pluripotent cells, mainly their specializing abilities, both in Petri dishes in a lab and when tested in animal models. However, primed cells are more limited in their pluripotency in animals.
August 25, 2022: The Dawn of Synthetic Embryos
Let’s now put all of our newfound knowledge to the test by taking a deep look at what synthetic embryos are.
There were actually two research groups who independently published their results showing synthetic mouse embryos can be created in August 2022. Though the two groups had shared information with one another while working on this project, they achieved their results through different methods.
The Hanna group created synthetic embryos using only one cell type, naive pluripotent stem cells, and they turned that cell type into the two other necessary ones — trophoblast stem cells and primitive endoderm cells. More specifically, these native pluripotent cells were mouse embryonic stem cells which are stem cells derived from mouse inner cell masses.
So how did they manage to turn these embryonic stem cells into other cell types? Through the magic of transcription factors!
Transcription factors are proteins that control what other proteins our cells produce, and therefore can change the identity of our cells. For instance, it’s in part due to transcription factors that our blood cells are different than our bone cells.
By adding more of certain transcription factors to the embryonic stem cells, the Hanna lab created trophoblast stem cells and primitive endoderm cells too.
After different lab processes were followed for each cell type, they were all put together and placed on certain Petri dishes. These dishes were put in an incubator to recreate the conditions needed for the synthetic embryos.
After 5 days, the synthetic embryos that were still developing properly were removed and placed in a roller culture system. This system provided the synthetic embryos with the necessary conditions and also — as the name suggests — rolled the embryos around, similar to a Ferris wheel.
They continued using this roller culture system until embryonic day 8.5, after which the synthetic embryos stopped developing as they should.
It’s important to note here that out of the many synthetic embryos that are initially created, very few go on to develop properly until embryonic day 8.5. In fact, only 0.1% to 0.5% of the initial synthetic embryos develop until then. As well, scientists did find some differences between natural embryos and synthetic ones.
Why Do We Need This?
The main reason these synthetic embryos are of interest is for studying the developmental process. It can be much easier to study embryos outside of the womb as scientists can more easily change their environment, what they’re exposed to and more, and study how these changes affect normal development.
Another application, which is still far off and requires much ethical discussion, is the use of synthetic embryos for transplantation. 450 Canadians die each year, waiting for an organ transplant, and this is an issue worldwide. The use of synthetic could help with that.
Is this Okay: The Ethical Dilemmas
For now, there are scientific challenges that bar researchers from creating synthetic human embryos and culturing synthetic mouse embryos for longer than 8 days. However, it’s important to assess what we, as a society, think is okay to do before we reach the scientific capacity to carry it out.
What do scientific organizations have to say about this? The International Society for Stem Cell Research had a guideline prior to 2021 saying that human embryos could not be kept in a lab for longer than 14 days.
However, in 2021, they changed these guidelines, saying that the so-called 14-day rule could be broken on a case-by-case basis if it is deemed absolutely necessary for the research purpose and is approved by a committee.
There is a great argument to be made for the creation of synthetic embryos as they offer a new way for researchers to understand normal development, and perhaps more importantly, how development goes wrong. The period between 14 and 28 days in human development is considered a black box and is difficult to study. Synthetic embryos could change that.
But, as many scientists have said, it’s critical to have discussions with the public before moving forward. There are some public engagement initiatives, but there’s still lots to be done to engage the public and get a diverse set of opinions on how we should move forward.
In short: there’s no easy answer as to how we should proceed with this new discovery. But one thing is for sure. Synthetic embryos can, with consensus from scientists and the public, offer many benefits to society.
About the Author
Parmin Sedigh is a 17-year-old stem cell and science communications enthusiast as well as a student researcher. She’s also an incoming first-year student at the University of Toronto, studying life sciences. You can usually find her on her computer following her curiosity. Connect with her on LinkedIn.