These human embryo-like structures (top) were synthesized from human stem cells; they’ve been stained to illustrate different cell types. Images (bottom) of the “embryoids” in the new device that was invented to make them. Yi Zheng/University of Michigan, Ann Arbor

Scientists have invented a device that can quickly produce large numbers of living entities that resemble very primitive human embryos.

Researchers welcomed the development, described Wednesday in the journal Nature, as an important advance for studying the earliest days of human embryonic development. But it also raises questions about where to draw the line in manufacturing “synthetic” human life.

Other scientists have previously created synthetic embryos, which are also known as embryoids. These entities are made by coaxing human stem cells to form structures found in very early human embryos. The research has raised questions about how similar to complete embryos they could and should be allowed to become.

The new work takes such research further by creating a method that can rapidly generate relatively large numbers of embryoids.

“This new system allows us to achieve a superior efficiency to generate these human embryo-like structures,” says Jianping Fu, an associate professor of biomedical engineering at the University of Michigan in Ann Arbor, who led the research.

Fu calls the step “an exciting new milestone for this emerging field” that should significantly improve the ability of scientists to study early human development.

“Such human embryo-like structures have a lot of potential to open what we call the so-called black box of human development,” Fu says.

He’s referring to the first few weeks after a sperm fertilizes an egg, when the embryo is inside a woman’s body and hard to study. A long-standing guideline bars scientists from conducting research on embryos in their labs beyond 14 days of development for ethical reasons.

Fu says the ability to produce large numbers of embryoids, which are not subject to the 14-day guideline, will hopefully provide scientists with new insights into important health issues, including how to prevent birth defects and miscarriages. In addition, researchers could use the embryoids to screen drugs, to help determine whether the medications are safe for pregnant women to take.

“Such research can lead to a lot of good,” Fu says.

Other scientists agree.

“It’s a major advance in the knowledge of early human development,” says Ali Brivanlou, an embryologist at the Rockefeller University in New York. “We’re opening up windows to aspects of development that we have never seen before. This knowledge is really the Holy Grail of human embryology.”

Other scientists and bioethicists agree. But they also caution that Fu’s research raises sensitive issues.

“I want to make 100% clear that we have no intention of trying to generate a synthetic structure [that] looks like a complete human embryo. We have zero intention to do that.” Jianping Fu, biomedical engineer, University of Michigan in Ann Arbor

“This team needs to be very careful not to model all aspects of the developing human embryo, so that they can avoid the concern that this embryo model could one day become a baby if you put it in the womb,” says Insoo Hyun, a bioethicist at Case Western Reserve University and Harvard Medical School.

Because of such concerns, Fu says he purposefully made embryoids that are not complete models of full human embryos. They only “resemble a portion of the human embryo — the core of the early human embryo,” Fu says. They are missing key structures, such as the early stages of the placenta and “yolk sac,” which provide nourishment to embryos.

“I understand that there may be people sensitive when you see that you can massively produce organized embryonic structures. People will be concerned. I understand that. I guess we are pushing the boundary,” Fu says.

The new device from the University of Michigan team enables scientists to rapidly produce large numbers of “embryo-like” structures. Human stem cells are first placed into the device; then chemicals are added to adjoining wells that stimulate the cells to grow key structures of human embryos.

“But I want to make 100% clear that we have no intention of trying to generate a synthetic structure [that] looks like a complete human embryo,” Fu says. “We have zero intention to do that.”

Others praised Fu’s approach, saying going further would be highly problematic.

“That would be sort of a very early sort of Frankenstein model, right? Taking different parts and stitching them together in order to try to create an organism,” says Daniel Sulmasy, a bioethicist at Georgetown University.

“If somebody tried to do it and it were even at the earliest stages of embryonic development, and they tried to then let it develop further, that would be a problem,” Sulmasy says.

The device Fu created is a thin silicone square. The plate contains four wells around a narrow channel. The scientists place stem cells — either human embryonic stem cells or induced pluripotent stem cells, which can be made from adult cells — into the device. Next, the researchers add to adjoining wells chemicals that stimulate the cells to grow key structures of human embryos.

Each device can produce about a dozen embryoids in just a few days, Fu says, and that enables the scientists to produce hundreds of the structures by using many of the devices simultaneously.


The Embryoids Growing

 Time-lapse video shows human stem cells forming “embryoids,” which include key structures of very early human embryos.

Credit: Yi Zheng/University of Michigan, Ann Arbor

The rapid advances in embryoid creation have prompted the International Society for Stem Cell Research to launch a review of its guidelines.

“If these embryo models end up being complete and are built to have all the components of natural embryos, they should be subject to the same 14-day rule that limits research with natural human embryos,” Hyun says. “That’s one more reason to avoid modeling the whole thing at once.”