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First 'blastoids' from mouse stem cells implanted in womb

21 October 2019
Appeared in BioNews 1020

US researchers have generated novel early embryo models – called blastoids – from mouse stem cells and implanted them into surrogate mice.

The study, which was published in Cell, described how a single type of mouse stem cell self-organised to generate the three tissue types that form a blastocyst. Scientists hope that these blastoids may aid understanding of embryo development and defects in early pregnancy.

'The embryo models could be studied in dishes to better understand early mammalian development, optimise IVF conditions and screen drugs for their potential to cause birth defects', said author Dr Jun Wu from the University of Texas Southwestern Medical Centre. 'Our goal is to have a scalable system for producing hundreds or even thousands of these embryo-like structures.'

Wu's team observed that extended pluripotent stem (EPS) cell lines, originated from either mouse embryonic cells or from ear skin cells, could self-organise into blastoids comparable to blastocysts at day 3.5. For this, the stem cells were cultured in a three-dimensional system, using appropriate cell culture media, and adding a range of growth factors and signalling molecules. 

The resulting EPS blastoids contained cells reflecting all three cell lineages found in embryonic blastocysts: the trophectoderm which gives rise to the placenta and the embryo-forming primitive endoderm and epiblast. 

'They essentially did the job on their own – you could see the cells that would become the placental tissue moving to the outside while others that would form the fetus moved to the inside,' Dr Wu said.

However, analysis showed that although gene expression in EPS blastoids was similar to blastocysts, there were some observable differences. Furthermore, when implanted into the uteruses of surrogate mice, EPS blastoids only induced malformed irregular placenta precursors and embryonic tissues, which did not develop into fetuses.

The authors hope to improve their protocol based on the observed differences so that fully functional blastoids can be established in the future. 

'The real holy grail is: can you do this with human stem cells,' Professor Janet Rossant from the University of Toronto – who was not involved in the study – told the Scientist. 'These stem cell–derived embryo models may not completely mimic normal development, but it might be enough to get you a little bit further in understanding the ways that the extraembryonic and the embryonic lineages can talk to each other in human development.'

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