Researchers have successfully shown that a method previously used for forming embryo-like structures in vitro using mouse stem cells, can be used to form embryo-like structures using a specialised type of human stem cell. Until recently, the study of human embryo development has largely relied on embryos voluntarily donated following IVF. To create the 3D model, researchers used human pluripotent stem cells (hPSCs) derived from embryonic cells which were then expanded in vitro. Remarkably, the stem cells retained the ability to self-organise into embryo-like structures.
'The ability to assemble the basic structure of the embryo seems to be a built-in property of these earliest embryonic cells that they are simply unable to "forget"', explained senior author Professor Magdalena Zernicka-Goetz at the California Institute of Technology. 'Nevertheless, either their memory is not absolutely precise or we don't yet have the best method of helping the cells recover their memories,' she clarified, referring to differences observed between the embryo-like structures and naturally formed human embryos.
Published in Nature Communications, the findings build on an array of recent studies modelling early embryo development with different types of stem cell (see BioNews 1088). The authors used hPSCs to recapitulate embryo development up until blastocyst formation, which occurs prior to implantation on the uterus wall. Their aim was to assess how closely the model could follow normal embryo development, where an initial cell mass differentiates into three cell lineages from which all human cells are derived.
Using RNA sequencing, Professor Zernicka-Goetz and her team compared each cell type in their model with their counterparts in natural embryos. They found that at most, roughly half of genes were expressed at comparable levels with natural human blastocysts, with no cell type expressing the full range of expected genetic markers. The team was unable to 'rescue' the developmental pathway by mixing the stem cells with fresh human embryo cells, which has previously worked in mouse models.
'We still have further work to do... to achieve the developmental accuracy that is possible with their equivalent mouse stem cell counterparts,' acknowledged Professor Zernicka-Goetz.
Despite genetic differences, the embryo models still appeared and behaved very similarly to early human embryos. Being derived entirely from stem cells, these models may also circumvent the strict 14-day limit on embryo study issued by the International Society for Stem Cell Research, which has recently updated its guidelines to account for advances in stem cell research.