Developmental biology: Human blastocyst-like structures generated in a dish

The generation of human blastocyst-like structures in the laboratory is described in a pair of papers published in Nature. The findings provide a model for studying early human development, and may lead to insights into early developmental defects, as well as aiding in the development of new in vitro fertilization (IVF)-associated therapies.

A few days after an egg has been fertilized, it develops into a blastocyst. This is a spherical structure made up of an outer layer of cells surrounding a fluid-filled cavity that contains a mass of embryonic cells. However, our understanding of early human embryonic development has been limited by a lack of appropriate models. Human blastocysts donated to research following IVF have provided insights, but their availability and use is limited. Recently, mouse blastocyst-like structures called blastoids have been produced in the laboratory, which model several aspects of early development in mice. However, the generation of similar blastoids from human cells has not previously been reported.

Jose Polo and colleagues reprogrammed human fibroblasts — the main cell type found in connective tissue — to produce three-dimensional models of the human blastocyst in the laboratory, which they called ‘iBlastoids’ (induced blastoids). The authors found that iBlastoids model the overall architecture of blastocysts and are capable of giving rise to pluripotent and trophoblast stem cells. They were also able to model several aspects of the early stage of implantation. However, they note that the iBlastoids should not be considered as an equivalent to human blastocysts.

In a separate study, Jun Wu and colleagues developed a three-dimensional culture strategy that allowed them to generate blastocyst-like structures, which they term ‘human blastoids’, from human pluripotent stem cells. The human blastoids resembled human blastocysts in their morphology, size, cell number and composition of different cell lineages. Human blastoids are able to generate embryonic and extraembryonic stem cells and can self-organize into structures with features of peri-implantation human embryos. In addition, the authors discovered the role of protein kinase C signaling in blastoid cavity formation. They emphasize that human blastoids are not equivalent to human blastocysts and are unable to give rise to a viable embryo.

Although these two models reproduce key aspects of early human development, they present a number of differences to actual human embryos and therefore should not be considered as such. Yi Zheng and Jianping Fu note in an accompanying News & Views that as protocols are optimized, these blastoids will more closely mimic human blastocysts, raising bioethical questions. “Thus, the continuous development of human embryo models, including human blastoids, calls for public conversations on the scientific significance of such research, as well as on the societal and ethical issues it raises.”