Lab-Grown Human Embryo Model
Esha Desai '28
About 60% of human pregnancies fail in the first fourteen days (Rossant & Fu, 2023). However, researchers aren’t able to observe embryos in a mother’s womb until they can be detected by ultrasound. Additionally, few people donate human embryos to science, and most countries prevent those embryos from being studied fourteen days after natural development. Scientists are solving this problem with stem cells that can be turned into embryo-like structures. Lab-grown embryos are a mass of stem cells grown in a laboratory that resemble part of early embryo development, and they break down easily after maturing in the earliest stages of development (Mallapaty, 2024). Embryo models are a new way to study how human embryos develop, the impact of genetic disorders on embryos, and the biological causes of recurring miscarriages (Devlin, 2023).
The first attempt at creating a “synthetic” embryo was in 2014, when researchers in the Zernicka-Goetz Lab separated embryonic stem cells into three germ layers that create cells to form the placenta and embryo (Warmflash et al., 2014). In 2023, scientists created new structures known as integrated embryo models. These were more advanced than past models since they contained tissue, not just cells, that are part of the human embryo, such as the yolk sac (Rossant & Fu, 2023). Having cells that develop into “extra embryonic structures” is important because they aid in the development of the embryo through providing nutrients and act as a pathway for gas to flow through from mother to child (Cleveland Clinic, 2022). Furthermore, because of supporting tissue in the “synthetic” human embryo design, these newer models show what the embryo will look like seven days after it is implanted in the uterine lining till the fourteen day mark where the embryo starts growing more tissue (Rossant & Fu, 2023).
There are many types of model embryos that resemble different stages of embryo development. Blastoids are model embryos that are similar to the first few days of embryo development. A fertilized cell during early parts of development forms a ball of “epiblast” cells, single cell layered tissues that later develop into all tissues of the human body (Sheng, 2015). These epiblast cells first form the embryo and extraembryonic cells that generate the placenta. To model this, blastoids are created by triggering differentiation and growth of human stem cells. Importantly, this process is easily replicable, making blastoids easy models to test chemicals for in vitro fertilization treatments. The second type of models mimicking phases of fetal development are called “post implantation models.” These models skip the implantation stage and are instead developed to model an embryo after fourteen days of development. These models are more intricate than blastoids because they include cells that support the membrane (yolk sac, placenta, amnion) of the embryo (Rossant & Fu, 2023).
Both of these models replicate the early stages of development impressively well, but they each have setbacks. Blastoids resemble the first few days of development of a natural embryo, but they fall apart when the embryo begins to implant itself onto the uterine wall. This is a particularly important step because the embryo undergoes a process called gastrulation, where the basic body plan—early brain, blood, placenta, and heart—forms (Rossant & Fu, 2023). A setback with these ‘post plantation models’ is that there is no control to test them for accuracy since scientists cannot use natural embryos for more than fourteen days. This creates a difficulty in gauging how close the model is to real embryo development.
The advancements of laboratory-grown models in recent years also pose numerous ethical questions. Should the same regulations on studying a real embryo be placed on a “synthetic” embryo? According to regulators, blastoids met the criteria of being considered
embryos under the definition of an embryo established by the International Society for Stem Cell Research: “biological entities with the potential to develop to a stage, roughly two weeks in, at which the structure called the primitive streak appears and the entity moves towards having a body plan” (Rossant & Fu, 2023). This means that scientists will have to treat blastoids like real embryos and abide by the same experimental guidelines. Thus, they have focused on creating models with enough differences from natural embryos so as to be classified differently. Laboratory-grown embryos provide new insight into the early developmental stages of embryos while raising ethical questions. Scientists, regulators, and lawmakers must collaborate to not stifle new, ethical research with human embryos models.
References
Cleveland Clinic. (2022, March 2). Yolk Sac in Early Pregnancy: Meaning & Function. Cleveland Clinic. https://my.clevelandclinic.org/health/body/22341-yolk-sac
Devlin, H. (2023, June 14). Synthetic human embryos created in groundbreaking advance. The Guardian.
https://www.theguardian.com/science/2023/jun/14/synthetic-human-embryos-created-in groundbreaking-advance
Mallapaty, S. (2024). Human embryo models are getting more realistic — raising ethical questions. Nature.com. https://doi.org/10.1038/d41586-024-02915-3
Rossant, J., & Fu, J. (2023). Why researchers should use human embryo models with caution. Nature, 622(7983), 454–456. https://doi.org/10.1038/d41586-023-03062-x
Sheng, G. (2015). Epiblast morphogenesis before gastrulation. Developmental Biology, 401(1), 17–24. https://doi.org/10.1016/j.ydbio.2014.10.003
Stem, A. (2023, August 5). About Stem Cells. About Stem Cells. https://www.aboutstemcells.org/info/embryo-models-rlrwl
Warmflash, A., Sorre, B., Etoc, F., Siggia, E. D., & Brivanlou, A. H. (2014). A method to recapitulate early embryonic spatial patterning in human embryonic stem cells. Nature Methods, 11(8), 847–854. https://doi.org/10.1038/nmeth.3016