Controversy resurfaces as scientists use human skin cells to generate complete embryo models

Two independent teams have found different ways to produce blastocysts – the stage of development about five days after an egg is fertilized – that could open the door to the future.

The scientists make clear that biological models, unlike human blastocysts, do not develop into embryos. But their work may have challenged new ethical guidelines in the biological sciences and could spark controversy.

In a detailed paper published Wednesday in Nature, the scientists argue that the model, known as a “blastocyst,” will help analyze issues such as miscarriage and the effects of toxins and drugs on early-stage embryos.

“We’re very excited,” said Jun Wu of the University of Texas Southwestern Medical Center, who led one of the teams, in a news release.” Human development research is really hard, especially at this stage, where it’s basically a black box.”

Currently, research on embryo development relies on donated blastocysts from IVF programs. But the supply is limited, and the material is only available to specific research institutions.

So the ability to generate unlimited “blastocysts” would be a game changer, said Jose Polo, a professor at Monash University in Australia who is leading another team.

“We think the ability to develop this on a large scale will revolutionize our understanding of the early stages of human development.”

Previously, techniques for generating blastocyst models have only been successfully applied to animals; in 2018 researchers successfully generated blastocysts in mice using stem cells.

The two teams differed slightly in their approaches.

Wu’s team used two different types of stem cells, some derived from human embryos and others from so-called induced pluripotent cells generated from adult cells.

Polo’s team, on the other hand, started with adult skin cells, but the end result for both teams was virtually the same: the cells began to organize into blastocysts with the three key components seen in human blastocysts.

“What was completely surprising to us was that when you put them together, they self-organized, they seemed to talk somehow …… and would consolidate themselves.” Polo said.

But while the models are similar to human blastocysts in many ways, there are also significant differences.

Both teams’ blastocysts ended up containing unknown types of cells, and they lacked some of the elements that come specifically from the interaction between sperm and egg.

The breeding success rate averaged only about 20 percent, though both teams said it represented a pathway to important research supplies.

The ethical debate

The scientists are at pains to state that these models should not be seen as pseudo-embryos, as they are not capable of developing into fetuses.

Still, they chose to err on the side of caution and end their study of blastocysts immediately after four days of Culture – the equivalent of about 10 days after fertilization in normal egg-sperm interactions.

The rules for studies involving human blastocysts set this deadline at 14 days.

These represent “exciting advances,” said Peter Rugg-Gunn, group leader at the Babraham Institute for Life Sciences Research in the United Kingdom.

Given the differences between blastocyst models and true human blastocysts, these models provide an adjunct but not a substitute for the existing donor pathway, said Teresa Rayon of the Francis Crick Institute at the Biomedical Research Center.