Review: gastruloids as model system to study embryonic development of mammals in a dish

Gastruloids mimic ‘gastrulation’; a process that takes place early during embryonic development and that ensures that all tissues and organs end up in the correct position within the developing embryo. Errors that occur during gastrulation can result in serious birth defects, highlighting the importance of reinforcing our understanding of this process. However, due to the ethical, legal and technical challenges associated the use of (human) embryos for research, our knowledge about gastrulation is currently limited.

Gastruloids: gastrulation in a petri dish

Gastruloids recapitulate aspects of gastrulation, and hence allow scientists to study the processes that take place during early embryonic development in a petri dish. Gastruloids can be generated from cells derived from various species, such as mice and fish, as well as from human embryonic stem cells. In their new review, published in Trends in Cell Biology, Susanne van den Brink and Alexander van Oudenaarden discuss the current status of the gastruloids field, with a focus on mouse and human gastruloid research.

Improved model

In recent years, various more complex versions of the mouse gastruloids system, which was first discovered in 2014, have been developed. Scientists recently for instance managed to develop mouse gastruloids that generate beating heart-like structures or that generate the precursors of the brain. It is currently however not possible to generate mouse gastruloids that form (the precursors of) the limbs. Furthermore, currently available versions of the mouse gastruloid system do not form extra-embryonic tissues. As such, the model cannot implant in the womb and does not have the potential to develop into a fully-formed embryo.

The first protocols to generate human gastruloids were developed more recently, and are therefore not as complex as the currently available mouse versions of the gastruloids system. Human gastruloids do for example not generate beating heart-like structures, nor do they contain any brain progenitor-like tissues. However, given the rapid developments in the field, it is not unlikely that further improved versions of human gastruloid models will be developed in the near future.

Applications

In their review, Susanne van den Brink and Alexander van Oudenaarden also discuss potential applications of the gastruloids model system. The system is currently already being used to study various aspects of embryonic development, and has recently provided fundamental new insights into for example the processes that regulate the shape of embryos or that regulate brain formation. Since gastruloids can relatively easily be generated in large numbers, the model system can probably also be used for toxicological screenings (large-scale studies that investigate which substances are toxic for developing embryos).

Furthermore, it should also be possible to use the model system to investigate the safety and effectiveness of new drugs or to identify new environmental or genetic causes of birth defects. Ultimately, it might even be possible to use gastruloids to generate cells or tissues for transplantation purposes in clinical settings in a dish.

Complex ethical issues

The currently available versions of the human gastruloids model conform to current ethical standards, but the recent developments in the field raise new ethical questions. When do human gastruloids for example become so advanced that their moral status becomes equivalent to that of the human embryo? And should informed consent be obtained from donors before their stem cells can be used to grow gastruloids? Scientist that are working in the gastruloids field are in close contact with ethicists to explore and discuss these emerging ethical and legal questions. The results of these discussions, which have recently led to new worldwide guidelines, will determine what avenues should or should not be pursued with human stem-cell based versions of this embryo model system.

Publication

van den Brink, S. C., & van Oudenaarden, A. (2021). 3D gastruloids: a novel frontier in stem cell-based in vitro modeling of mammalian gastrulation. Trends in Cell Biology.