An international group of 14 scientists, coordinated by Alfonso Martínez-Arias from the Department of Medicine and Life Sciences, Pompeu Fabra University (MELIS-UPF), has established criteria to help define stem cell-based embryo models that will be useful for future research.
These novel models mimic the early stages of human development, a period that is difficult to study because of significant ethical and technical challenges. “The restrictions on using human embryos mean that our knowledge about human development between day 14 and week 4 is very limited,” explains Susanne van den Brink, researcher at the Hospital del Mar Research Institute.
“Embryo models” or “embryonic organoids“, which are three-dimensional structures that mimic human embryos, can recapitulate early developmental events like tissue patterning and morphogenesis. These events cannot be studied otherwise, but are crucial for understanding fertility problems and newborn anomalies.
“False” embryo models
However, “sometimes claims are made about structures that are supposedly embryo models, but in reality, they do not mimic the embryo,” explains Martínez-Arias, “which can lead to knowledge errors.” This is because it is a very new field, and there is a lack of criteria to follow.
Embryo models are three-dimensional structures that mimic human embryos. An expert group has proposed the characteristics they should have to be reliable.
For this reason, a small group of stem cell and developmental biology experts from around the world has been working for a year to establish the necessary characteristics to ensure that these embryo models are reliable. In a comment in Nature Cell Biology, the expert group proposes standardizing the rules for creating, characterizing, and evaluating human stem cell-derived embryo models.
“Our goal is to clarify what should be called an embryomodel so it can be used in research and reproductive biology,” says Martínez-Arias, ICREA researcher and one of the leaders of the work. “A range of attributes is required, but I think the most important thing is that they must resemble the whole or parts of the embryo and, most importantly, like the embryo, they must be reproducible. We cannot call something a model if it produces different structures in every experiment,” he explains.
For Martínez-Arias, the current benchmarks for embryonic models are “blastoids,” which mimic the blastocyst, and “gastruloids,” which mimic stages after gastrulation.
“If our suggestions for these guidelines are adopted, we will be able to prevent misunderstandings that are very harmful to the potential of this new but important field”
Alfonso Martínez-Arias, MELIS-UPF
“When you mix embryonic stem cells, things happen, and among them, you can find structures that more or less make sense. There are several works of this type in high-visibility journals. But this doesn’t mean that these structures have anything to do with embryos”, the researcher explains. “In fact, the biggest problem these structures may have is when they are applied to clinical uses, or more honestly, preclinical uses, as they may lead to misuse“, he concludes.
The initiative seeks to ensure a common vocabulary, agreeing on definitions of several concepts, and improving communication between researchers, media, and society. It also aims to help funding bodies and regulators assess this promising field.
“I hope the journals publishing these works and the national regulatory bodies take these suggestions into account because we definitely need to raise the standard of the field“, concludes the MELIS-UPF researcher.
To learn more about embryo models, you can watch this video (in Dutch and English) about the work being carried out by Susanne van den Brink in the lab led by Anna Bigas at the PRBB:
Martinez Arias, A., Rivron, N., Moris, N. et al. Criteria for the standardization of stem-cell-based embryo models. Nat Cell Biol (2024). https://doi.org/10.1038/s41556-024-01492-x
