December 2, 2021

expert reaction to study demonstrating a new model simulating human embryo development

A study published in Nature uses human blastoids to model blastocyst development and implantation.

Dr Harry Leitch, Stem cell biologist and group leader at the MRC London Institute of Medical Sciences, and Academic Clinical Lecturer in Clinical Genetics, Imperial College London, said:

“In 2018, the authors of this study pioneered the use of mouse stem cells to generate structures that resemble the blastocyst stage of pre-implantation development. While these so-called ‘blastoids’ did have some features of normal embryos, they could not progress in development to post-implantation stages. Since this time, a number of labs have reported different protocols to generate blastoids using human stem cells, and this study represents another important contribution to the field. This may be a useful system to study human developmental biology but, as in the mouse, further work will be needed to clarify if these stem cell models can progress in their development to the stages when the early progenitors of different tissues form.”

Prof Robin Lovell-Badge FRS FMedSci, Group Leader, The Francis Crick Institute, said:

“This paper represents further steps on the way to develop stem cell-based models of early human embryos, with the authors providing data to suggest that their blastocyst-like structures (or blastoids) can attach to endometrial cells in a way that may mimic normal implantation into the uterus.

“The structures could continue some aspects of development up to 13 days that again resembled how normal blastocysts can develop in similar cultures. However, this does not mean that they would be able to develop normally into a later stage embryo or fetus if they were to be transferred into a person’s uterus. Indeed, there were sufficient differences in the cells present and the gene activity in comparisons between these developing blastocyst-like structures and the rather few normal embryos that have been studied in a similar way to suggest that this would be impossible. It would also be illegal to attempt this in the UK. Given the differences between human and non-human embryos, we also cannot rely on the latter for validation of the human stem-cell derived embryo-like structures.

“To really know whether these or other stem cell-based embryo-like structures can be used to accurately model aspects of normal human embryo development will require detailed comparisons with normal human embryos, and preferably their culture to stages beyond 14-days when the complexity that characterizes the gastrulating embryo begins to develop. However, if validated, this would reduce the need to work directly with human embryos.”

Prof Magdalena Zernicka-Goetz FMedSci, Professor of Mammalian Development and Stem Cell Biology, University of Cambridge, said:

“There has been remarkable progress in our ability to generate embryo-like structures from stem cells. However attempts to generate blastoids – replicas of human blastocysts, the ball of cells of the 7-day old embryo – have been hindered by the inability to form structures that faithfully replicate the three cell types in natural blastocysts. A particular difficulty has been in generating trophectoderm (TE), the extra-embryonic cell type that will form the placenta.

“In this new study, TE cells are generated by treating pluripotent human stem cells with inhibitors to block three signalling pathways – the Hippo, TGF-β and ERK pathways – whose inhibition is known to drive naïve human pluripotent stem cells (hPSCs) to form TE. By inhibiting these three pathways, the authors have overcome this major hurdle and are able to generate blastoids that form all three pre-implantation cell lineages and recapitulate the gene expression patterns of natural blastocysts. Excitingly, when these blastoids are co-cultured with endometrial organoids that can mimic the natural cell lining of the uterus and be stimulated to be responsive to implantation, they model the first stages of the interaction of the blastocyst with maternal tissue. The system promises to be widely applicable for the study of the basic biology of the earliest stages of human pregnancy and for practical applications such as the development of novel contraceptives.”

‘Human blastoids model blastocyst development and implantation’ by Nicolas Rivron et al. was published in Nature at 16:00 UK time on Thursday 2^nd December 2021.

DOI: 10.1038/s41586-021-04267-8

Declared interests

Dr Harry Leitch: “No conflicts of interest.”

Prof Robin Lovell-Badge: “Robin Lovell-Badge has no financial conflicts of interest to declare, he does, however, serve on the Scientific and Clinical Advances Adviosrty Committee for the HFEA, and he chaired the taskforce responsible for the 2021 updates to the ISSCR Guideline on Stem Cell Research.”

Prof Magdalena Zernicka-Goetz: “No conflicts to declare.”