Scientists from University of Cambridge have created a structure derived from mouse stem cells that is capable of self-assembling to closely resemble a real mouse embryo.
After fertilisation, mouse embryos undergo several cell divisions to form a ball of cells called a blastocyst. At this stage of development, cells become segregated into distinct regions; the trophectoderm, which is fated to become the future placenta, and the inner cell mass, which will give rise to the embryo. Trophoblast stem cells (TSCs) and embryonic stem cells (ESCs) can be derived from the trophectoderm and inner cell mass respectively and propagated in culture.
This study, published in Science, used TSCs and ESCs grown in a 3D scaffold to form embryo-like structures. The artificial ‘embryos’ were cultured for seven days – the equivalent of a third of the period of mouse pregnancy. At this stage, the structure had self-organised into two distinct sections, morphologically resembling the regions from which the placenta and the mouse embryo would form in a natural embryonic develop.
Previously, embryoid bodies, derived from ESCs, have been used as a model for development as they can be induced to express genes in a pattern resembling those expressed in early post-implantation embryos. However, although gene expression patterns may be similar, embryoid bodies are not anatomically similar to embryos and do not follow the same spatial-temporal events.
Professor Magdalena Zernicka-Goetz and colleagues hypothesized that this may be because the ESCs lack signals from the extra-embryonic tissues that guide organization during implantation. Indeed, it appears to be the communication between the TSCs (derived from extra-embryonic tissue) and the ESCs that triggers the structure to self-assemble to resemble embryos.
The artificial embryo exhibited anatomically accurate regions that developed correctly both spatially and temporally. However, despite the strong similarities with real embryos, the researchers have said that the artificial embryo is unlikely to be able to develop further into a healthy fetus, as the artificial embryo lacks an additional population of cells (termed the primitive endoderm) that gives rise to the yolk sac, which acts to provides nourishment for the embryo and is important for early embryonic blood supply.
Professor Zernicka-Goetz has stated that the goal of their research is not to produce mice outside the womb but rather to shed light on the relatively unknown mechanisms of development that operate before the embryo has implanted into the mother’s uterus. Up to two-thirds of miscarriages are thought to occur prior to implantation so it is hoped that these artificial embryo-like structures will allow scientists to gain more insight into this critical stage of development.
Thus, to better understand human development, the research team are hoping to build on this work to create similar artificial embryos using human stem cells. However, they face a major barrier in accomplishing this due to the fact that whereas TSCs can be readily derived from mouse blastocysts, attempts in human blastocysts to derive similar stem cells have failed so far.