03.07.2023 | Stem cell research
In the last 10 years, many embryo models have been developed in laboratories. This means shaping human stem cells into balls, smaller than the diameter of a hair. These models do not resemble embryos and are not legally or scientifically considered as such, but they are increasingly important for laboratory research into how embryonic cells organize themselves and what genes and molecules are involved. Additionally, they offer an ethical alternative to research on human embryos developed from artificial insemination. In some countries, these can be donated to science by parents who no longer wish to have children, as Nicolas Rivron of the IMBA - Institute of Molecular Biotechnology of the Austrian Academy of Sciences describes.
What are embryo models exactly?
Nicolas Rivron: Over the past decade, embryo models have been formed in the laboratory by aggregating animal or human stem cells into a ball, smaller than a hair’s diameter. Under certain conditions, these models can partially mimic aspects of early embryonic development, such as the ones occurring during the first week of pregnancy. It is important to note that embryo models are far from being similar to embryos and are not legally or scientifically considered as such. Nonetheless, in the laboratory they are extremely useful for researching how embryonic cells organize themselves and which genes and molecules play a role in this process, thereby answering important scientific and medical questions.
How do embryo models differ from embryos created from a fertilized egg?
Rivron: They are formed from stem cells, thus theydon’t require the use of egg and sperm, but they are far more simplistic and less organized than embryos and that is why it is important to call them embryo models. In the case of animal embryo models, they are incapable of developing into an animal. In fact, they can only develop for a few days.
They are incapable of developing.
Does research on embryo models represent an alternative to research on embryos?
Rivron: Over the last 50 years, in many countries, but not in Austria, embryos obtained through in vitro fertilization (IVF) have been generously donated by parents who have completed their parental project. These donated IVF embryos, typically consisting of around 100 cells, can be used in highly specialized laboratories after receiving approval and under strict monitoring by ethics committees. Researchers can study how they function, for example, by exposing them to, say a specific hormone to improve their ability to implant in the uterus. However, research must stop on day 14 of development. Since IVF embryos are scarce, their use is limited and complicated. In contrast, embryo models can be easily formed without the need for embryos, thereby offering an ethical alternative.
Embyromodelle können Erkenntnisse liefern, die zur Verbesserung von In-vitro-Fertilisation oder zur Verhinderung von Fehlgeburten wichtig sind."
What advances have you made recently in embryo models?
Rivron: We have identified some molecules that were not known to be present in the uterus and that we think support the development of the embryo. These molecules might prove useful for medical applications to improve IVF outcomes or prevent pregnancy loss, and we hope we can test them further.
Can you give us an insight into the development of an ethical framework (for the research on embryo models?) in which you are involved?
Rivron: All the research in this field is subject to rigorous oversight by international, EU and national ethics committees. In Austria, the Commission for Science and Ethics of the Austrian Academy of Sciences (OeAW) has concluded that the research is scientifically promising and does not conflict with ethical principles defined in Austrian and EU regulations. They also judge that we have sufficient knowledge and experience to conduct this research with the high standards that are necessary.
All the research in this field is subject to rigorous oversight by international, EU and national ethics committees."
In addition, through discussions with scientists, ethicists, philosophers, and regulators in many countries, as well as with the International Society for Stem Cell Research (ISSCR), I have been actively involved in strengthening this ethical framework surrounding this research. This strict regulation and monitoring ensure that the research progressively delivers findings that will hopefully translate into medical progress.
At a glance
Nicolas Rivron is leading a research group conducting research with embryo models at IMBA - Institute of Molecular Biotechnology at the Austrian Academy of Sciences (OeAW). Previously, he has worked at various scientific institutions in the Netherlands and the USA. In 2020, he received a Consolidator Grant from the European Research Council (ERC) for his research work.
What are embryo models used for in research?
Embryo models are important for studying early embryonic development and could contribute to addressing global health challenges, including reproductive health in an aging population and prenatal preventive medicine to ensure a baby’s health.
What possible applications do researchers hope to discover using embryo models?
It is about improving reproductive health and prenatal preventive medicine, that is, the baby’s and mother’s health. For example, using embryo models, we can identify naturally occurring molecules in the uterus that could improve the formation and implantation rate of IVF embryos. Finding these molecules could reduce the number of fertilized eggs and the number of cycles required to achieve a successful pregnancy. It may also be possible to prevent abnormal embryo implantation that leads to early miscarriages, for example due to ectopic or molar pregnancies. This knowledge could also contribute to the development of nonhormonal contraceptives with fewer side effects. Finally, it could help us understand the origin of the baby's health.
What advances have researchers made recently in embryo models?
Research groups worldwide have successfully developed mouse, cow, monkey, and human embryo models. These models are currently being used to understand human-specific aspects, particularly why human pregnancies fail more often than in other species.
What are the guidelines for embryo model research in Austria?
Currently, laws in Austria covering embryo research do not extend to research on embryo models. Researchers adhere to the guidelines of the European Union, the International Society for Stem Cell Research (ISSCR), and any proposed work is assessed in advance by the Commission for Science and Ethics of the Austrian Academy of Sciences (OeAW).
What are the legal guidelines set by the International Society for Stem Cell Research (ISSCR)?
The ISSCR guidelines state that research on embryo models should only proceed when there is a compelling scientific rationale and after undergoing review and approval by a specialist oversight process. The embryo models should be cultured for the minimum time necessary to achieve the scientific objectives. Finally, it prohibits the transfer of human embryo models into any uterus, whether animal or human. These strict regulations promote scientific progress that will eventually benefit society, while preventing unethical research paths.