Two research groups have now generated human blastocyst-like structures from cells in a dish. This valuable model provides hope of advancing human embryology.
Human embryo
Simple stem cell models, such as human pluripotent and trophoblast stem cells, have been invaluable alternatives to blastocysts for developing our understanding of early human development. However, these simple culture systems lack the ability to adequately model the complex spatiotemporal molecular changes that occur during early embryonic development. Currently, the only way to study this is to incorporate information from blastocysts that have been donated to research following IVF. Nonetheless, limited access to embryos and the complex ethical and legal constraints has hampered the study of human embryogenesis and disorders that occur during early pregnancy.
The recent emergence of techniques that use cells cultured in vitro to reconstruct models of mammalian embryos have opened up exciting opportunities to study human embryology. Researchers have produced in vitro integrated models of mouse blastocysts, called blastoids, using two different approaches. The first involves assembling pre-established stem cell lines and the second, involves differentiating extended (or expanded) pluripotent stem cells into blastocyst-like structures. Until now, the generation of similar blastoids from human cells has not been achieved. Two papers now published in Nature, have shown that human embryonic stem cells or cells reprogrammed from adult tissues can be induced to self-organise in a dish, forming structures that resemble the early human embryo.
Human blastoids
Both papers, Yu et al. and Liu et al. describe human blastoids. Yu et al. began with naïve human pluripotent stem cells, which the researchers isolated from human blastocysts or generated by reprogramming adult human cells. By contrast, Liu et al. reprogrammed adult skin cells (fibroblasts) to form a mixed cell population that contained cells with gene-expression profiles similar to that of the epiblast, trophectoderm and hypoblast (found in blastocysts). The team termed these models iBlastoids.
Both teams found that human blastoids emerged 6-8 days after culture, with a formation efficiency of almost 20%, comparable to that of the mouse blastoid protocols. In addition, the human blastoids were of a similar size and shape to natural blastocysts, with a similar total number of cells. Both teams also performed detailed characterisation of the blastoids, revealing that their cell lineages share molecular similarities with those of the pre-implantation human blastocyst.
The researchers also analysed the development of the blastoids using an assay that mimics implantation into the uterus in culture dishes. Like blastocysts, when blastoids were grown, some attached to the culture dish and continued to develop. Some of these blastoids reorganised into structures reminiscent of the pro-amniotic cavity, whilst others spread out and showed signs of differentiation into specialised placental cell types.
Overall, human blastoids provide a readily accessible, scalable and tractable alternative to blastocysts for studying early human development as well as pregnancy-related disorders and IVF. Nonetheless, as researchers optimise these protocols, the blastoids will more-closely mimic human blastocysts. This will ultimately provoke questions surrounding bioethics, which will call for public conversations on the scientific significance of such research.
Image credit: By Science Photo Library – canva.com
