Fertilization of the egg by a sperm marks the beginning of human embryogenesis, the entire developmental process that transforms the zygote into a fetus. The first 15 days of embryonic development, before the embryo implants in the uterine lining, remain difficult for scientists to study because the first human embryos available for research are quite rare.
Two teams, one at the University of Texas Southwestern Medical School led by embryogenesis expert Jun Wu, and the other at Monash University in Australia, have succeeded in creating human embryos at the blastocyst stage from cells grown in the laboratory. This technique has already been used with mouse embryos but is completely new with human cells.
A five-day-old human embryo created in vitro
Immediately after fertilization, the zygote is transformed by cell division. It first contains two cells, then four, then eight, and so on. On the fourth day, it reaches the blastocyst stage. The cells, which until then were all identical, divide into two populations according to their location: those on the outside become the trophoblast and those on the inside become the cells of the inner mass (embryoblast). The next few hours were crucial for the latter, which again divided into two distinct populations: the cells of the inner mass become epiblasts or hypoblasts (or primitive endodermis). These three cell types organize around a cavity, the blastoceles. At this stage, the blastocyst implants into the uterus to continue its development.
Both research teams were able to recreate human blastocysts from cultured cells. The Texas team used pluripotent stem cells in its lab. The second team started from a different base, reprogrammed adult fibroblasts. The rest of the protocol is similar for both groups, growing the cells in a special dish where they develop into organoids in a culture medium that contains all the chemical elements necessary for the formation of blastocysts. After about a week of culture, the two teams obtained human blastoids comparable in size, shape, and organization to natural human blastocysts.
A promising study model
The experiments didn’t stop there. The scientists wanted to further analyze the development of their blastoids by mimicking implantation in the uterus in vitro. After four or five days of culture, some blastoids adhered to the culture dish, and some cell populations continued to differentiate. Trophoblasts begin to specialize into placental cells and epiblast cells reorganized around the cavity.
Thus, these blastoids, which are very similar to natural blastocysts, appear to be promising in vitro models for studying early embryonic development and associated diseases but remain imperfect for now. Obtaining these blastoids is laborious and difficult to reproduce. In addition, the three cell populations do not develop synchronously within the same blastoid, and blastoids from the same experiment do not develop at the same rate. Finally, scientists have identified cell populations in organoids that are not found in natural blastocysts.
The study of blastoid development will go no further because ethics prohibit the culture of human embryos beyond 14 days of development. At this stage, after gastrulation, the first tissues that form the fetus appear. These lab-made human blastoids are the first human embryo models derived from cell culture that have an organization and development comparable to natural blastocysts.