Laboratory-made human embryo models

In the first week, a fertilized human egg develops into a hollow ball of 200 cells and then attaches itself to the wall of the uterus. Over the next three weeks, it breaks down into the individual tissues of the human body.

And these crucial weeks remain largely a black box.

“We know the basics, but we just don’t know the very fine details,” said Jacob Hanna, a developmental biologist at the Weizmann Institute of Science in Israel.

dr Hanna and a number of other biologists are trying to uncover these details by creating models of human embryos in the laboratory. They cause stem cells to organize into clumps that take on some of the defining characteristics of real embryos.

This month, Dr. Hanna’s team in Israel, as well as groups in Britain, the United States, and China, report on these experiments. Although the studies have not yet been published in scientific journals, they have sparked great interest from other scientists who have hoped for years that such advances could finally shed light on some of the mysteries of early human development.

Ethicists have long warned that the introduction of embryo models would further complicate the already complicated regulation of this research. However, the scientists behind the new work were quick to point out that they had not created true embryos and that their stem cell clusters could never give rise to a human.

“Our goals are never for human reproduction,” said Tianqing Li, a developmental biologist at Kunming University of Science and Technology in China, who led one of the new studies.

Instead, Dr. Li and his fellow scientists predict that embryo models will lead to new treatments for infertility and even diseases like cancer.

“We’re doing it to save life, not create it,” said Magdalena Zernicka-Goetz, a developmental biologist at the University of Cambridge and the California Institute of Technology, who led another initiative.

For decades, the only human embryos developmental biologists could study were samples from miscarriages or abortions. This led scientists to ask profound questions about the beginning of human development. Thirty percent of pregnancies fail in the first week and another 30 percent fail during implantation. Researchers couldn’t explain why most embryos don’t survive.

After the development of in vitro fertilization in the 1970s, scientists began studying embryos donated from fertility clinics. Some countries have banned the research, while others have allowed it to continue, usually with a 14-day notice. At this point, the human embryo begins to take on some of its most important characteristics. For example, a structure called “Primitive Streak” organizes the head-to-toe arrangement that the body will adopt.

For years, the 14-day rule was controversial because nobody could keep embryos alive longer than a few days after fertilization. Things got more complicated in 2016 when the group of Dr. Zernicka-Goetz and another team managed to keep embryos alive near the 14-day mark. The embryos no longer survived because the scientists destroyed them.

This achievement has prompted scientists to discuss the possibility of growing embryos longer than 14 days. But even if these experiments became legal, they would still be difficult to conduct due to the scarce supply of donated embryos.

In recent years, researchers have been looking for an easier way to study embryos: by making models of them in the laboratory. The scientists took advantage of the fact that stem cells can transform into novel tissues under the right environmental conditions.

Adults only have stem cells in a few parts of the body. In the skin, for example, stem cells produce a series of new cells that heal wounds. In early embryos, on the other hand, all cells have the potential to transform into a wide variety of tissues.

Last year, the team of Dr. Zernicka Goetz and Dr. Hanna used mouse embryonic stem cells to create models of embryos. Since then, she and other scientists have been trying to do the same thing with human embryonic stem cells.

Each team used a different method, but all use the same underlying biology. When a human embryo implants itself in the uterus, its cells begin to break down into different types. One cell type will continue to produce the body’s cells. The other types produce tissues that surround the embryo during development, such as the placenta. These cell types send each other molecular signals that are essential for their development.

The researchers got stem cells to mimic some of these cell types and then mixed them together. The cells swarmed together and spontaneously organized into clusters. The cells from which the embryo would develop crowded in the center while the other species migrated outward.

As the cells communicated with each other, they divided and formed new structures that resembled parts of embryos. dr In their experiment, for example, Mo Ebrahimkhani, a developmental biologist at the University of Pittsburgh, and his colleagues observed the formation of a yolk sac. They even observed the development of progenitor cells of blood cells from the yolk sac.

also dr Zernicka-Goetz and her colleagues observed the development of cells that resembled the progenitors of egg and sperm.

“It was absolutely exciting,” said Dr. Zernicka-Goetz. “Sometimes it’s hard to believe that these stem cells grow into these structures.”

If scientists can create accurate, reliable models of embryos, they can conduct large-scale experiments to test possible causes of pregnancy failure, such as viral infections and genetic mutations.

The models could lead to other medical advances as well, noted Insoo Hyun, a member of the Harvard Medical School Center for Bioethics who was not involved in the new studies.

“Once you have the embryo models installed and can rely on them, it can be an interesting way to test drugs that women take during pregnancy,” he said. “That would be a huge benefit.”

dr Hannah and Dr. Ebrahimkhani also saw an opportunity to use embryo models as a new form of stem cell treatment for diseases such as cancer.

In traditional stem cell transplants, doctors remove blood stem cells from the bone marrow before using radiation or chemotherapy to kill cancer cells. They then return the healthy cells to the body.

Unfortunately, this method does not have a high success rate. Some researchers have suggested that earlier forms of stem cells would be more likely to cure patients.

Embryo models could allow doctors to turn back time. Researchers would take skin cells from a patient and douse them with chemicals to turn them into a stem cell-like state. Using other chemical baths, these stem cells could then be transformed into an embryo model, which in turn could develop into the early blood cells that the patient will need after a transplant.

Alysson Muotri, a developmental biologist at the University of California San Diego who was not involved in the new studies, warned that the new studies only show a preliminary step. On the one hand, while the techniques sometimes resulted in embryo-like clusters, they often failed.

“The work is at a very early stage and the current methods are far from reliable,” said Dr. Muotri.