Scientists create first complete human embryo model in Petri dish

The early stages of human embryo development are difficult to study due to a lack of availability and ethical and legal constraints. Now scientists have created the first ever complete human embryo model in a Petri dish.

Scientists in the US and Australia have created the first human embryo models in Petri dishes, according to a report in the British scientific journal Nature.

The report takes the findings of two studies that show human embryonic stem cells or cells reprogrammed from adult tissues can be induced to selforganize in a Petri dish, forming structures that resemble early human embryos.

In the early stages of development, human embryos form a structure called the blastocyst. The researchers have created human blastocyst-like structures or "blastoids" from cells in a Petri dish.

It is the first integrated human embryo model to contain cell types that relate to all the founding cell lineages of the fetus and its supporting tissues, the report stated.

The human blastoids could be an accessible, scalable alternative to blastocysts that could help to improve assisted reproductive technologies, insights into early development and prevent pregnancy loss and birth defects, the studies stated. Barriers to embryo research Studying the early development of a human embryo can be difficult due to the limited number available and ethical and legal constraints.

The International Consensus and National law for culturing human embryos states that embryos obtained by IVF can be cultured up to 14 days post-fertilization and/or the formation of a primitive streak, whichever is first, the Australian study said.

"The applicability of the '14day rule' to in vitro models of early development that are not derived by fertilization is not clear," the authors wrote. This led the team to be cautious and only culture the blastoids for up to five days.

Thomas Zwaka, a professor in the Department of Stem Cell and Developmental Biology at the Icahn School of Medicine in New York, said the availability of an alternative model will reduce the pressure on researchers to use real human embryos in research

"There are still many unsolved mysteries at this stage of early human development, which lays the foundation for almost all processes, organs and, unfortunately, diseases," Zwaka told the Science Media Center Germany. "That's why there is an urgent need for a method like blastoids that opens this door a little wider, even if it's not perfect."

How the embryo forms

In humans, a few days after fertilization, the egg forms a structure called the blastocyst. This structure has an outer cell layer called the trophectoderm which surrounds an area that houses the inner cell mass (ICM). As the blastocyst develops, the ICM splits in two cell types groups — the epiblast and hypoblast.

The blastocyst then implants into the uterine tissue where gastrulation will eventually happen — this is when epiblast cells pave the way for the development of cells that will form the entire fetus. The trophectoderm goes on to form most of the placenta and the hypoblast helps to form the yolk sac, which is needed for early fetal blood supply.

An important step for science

Both the US and Australian scientists found that human blastoids emerged after 6–8 days of culture, with a formation efficiency of up to almost 20%.

The blastoids had a similar size and shape to the natural blastocysts, as well as a similar total number of cells. They also contained a cavity and an ICMlike cluster.

The researchers then looked at how the blastoids developed when implantation into the uterus was mimicked in culture dishes, the report stated. Similarly to blastocysts, when they were grown for four to five days, some attached to the culture dish — and some of these showed signs reminiscent of a pro-amniotic cavity and placental cells.

Previously, models of early human development have used human stem cells that were developmentally similar to postimplantation, pre-gastrulation cells, according to the report. But while they could repeat some states of post-implantation human development, sometimes they didn't have lineages associated with the trophectoderm, hypoblast or both — all of which are essential for the development of a baby.

Nicolas Revron, a group leader at the Institute of Molecular Biotechnology in Vienna, said it was essential that the blastoids were able to form the first three cell types of the embryo: the epiblast, trophoblasts and the hypoblast.

"There is evidence that there are some cells that resemble these three cell types, but there are also many differences, and other cell types as well," Rivron told the Science Media Center Germany.

Blastoids are not blastocysts

The studies do have limitations. The development of the blastoids is inefficient and varies depending on the cell lines produced from different donors. The blastoids also contain unidentified cell populations that are not found in natural human blastocysts.

Development of the blastoids is also limited in post-implantation stages and the culture and experimentation conditions will be needed to improve postimplantation-stage culturing of human blastoids in vitro up to the equivalent of 14 days in vivo, the report stated.

This is a real human blastocyst. Researchers have now created similar structures or "blastoids".