Embryo models generated from human stem cells have provided insights into how identical twins develop.

Blastoids are stem-cell-based embryo models (SCBEMs) that resemble embryos at the blastocyst stage (see BioNews 1020, 1088, 1091, 1124, 1204). Researchers at the MERLN Institute for Technology-Inspired Regenerative Medicine, at Maastricht University in the Netherlands, have studied the conditions under which single blastoids and 'twin' blastoids can form. Currently, little is understood about the mechanisms that lead to the formation of monozygotic twin embryos, which is something that occurs more frequently following IVF and that can be associated with pregnancy complications.

'Blastoids are stem-cell-derived in vitro models of the blastocyst stage of embryogenesis,' Dorian Luijkx, from the MERLN Institute and lead author of the study published in Advanced Materials, explained.

To generate blastoids, the researchers seeded stem cells into parallel microwells with transparent walls, which are flat plates with multiple wells used as small test tubes. Within each well, the stem cells clustered together to form structures which the researchers monitored and imaged as they grew. By adding a different combination of growth factors and chemicals to each well, the researchers were able to optimise the conditions for growing twin blastoids on a large scale.

The researchers found that seeding a higher number of stem cells per microwell increased the formation of twin blastoids. They also found that adding a high concentration of chemicals to promote stem cell differentiation into the trophectoderm, which is the outer layer of a blastocyst that goes on to form the placenta, increases the formation of twin blastoids. For this reason, the researchers suggest that rapid expansion of the trophectoderm may be a crucial event leading the inner cell mass to split and form twin blastoids. A similar process may be at work when twinning occurs during the development of embryos.

'We aim to delve deeper into the molecular and biophysical mechanisms that underlie the splitting of the inner cell mass, as these may give us clues as to how twinning rates in assisted reproductive technology can be reduced or completely avoided,' Dr Stefan Giselbrecht, one of the senior authors of the study, said.

To study embryo implantation, single and twin blastoids were moved to a microfluidic chip that contained a small sample of uterine tissue. The scientists noted that the twin blastoids adhered to the uterine tissue at a higher rate than the single blastoids, which Dr Giselbrecht added 'may suggest an advantage for a twin embryo in the implantation stage of development'.

Because blastoids and other SCBEMs are similar to but also different from human embryos, they can pose distinct ethical and regulatory challenges. Last year, the Health Council of the Netherlands recommended that some SCBEMs should be subject to the same regulation as human embryos, while other SCBEMs should not (see BioNews 1214).

In the UK, a project is underway to develop a recommended governance framework for research involving SCBEMs (see BioNews 1194). As part of this project, a public dialogue report has been published exploring what members of the public think and know about SCBEMs (see BioNews 1234). This report is due to be followed by the publication of a Code of Practice for UK research involving SCBEMs.

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Stem-cell-based embryo models used to study human twinning PET - BioNews