Mijo Simunovic, Ph.D., Simon's Junior Fellow, The Rockefeller University
Scientists have created living things that resemble primitive human embryos, the most advanced example of this structure ever created in a laboratory.
The researchers hope that these creations from human embryonic stem cells will provide important new insights into human development and lead to new ways to treat infertility and prevent miscarriage, birth defects and many diseases. The researchers say this is the first time scientists have created living models of human embryos with three-dimensional structures. The researchers reported their findings on Monday in an article published in the journal Nature Cell Biology]
But research is a heated debate about how far scientists should go to live models of human embryos, sometimes called embryoids to manufacture.
"It's a very exciting work," says Insoo Hyun, bioethicist at Case Western Reserve University and Harvard Medical School, who was not involved in the research. "But it makes people think very seriously about the ethical limits to this work."
For decades scientists have been working to understand some of the earliest steps that allow an embryo to become a  fetus. However, some of the most important early steps were a mystery. This is because they occur in the womb of a woman and can not be examined. Scientists are forbidden to examine human embryos after 14 days of development in their laboratories.
As a result, these very early stages of development were "a complete black box," says Ali Brivanlou, molecular biologist at Rockefeller University, New York, who heads the lab where the new research was conducted.
So Brivanlou and his colleagues decided to use human embryonic stem cells to create living models of human embryos that they could examine in the lab.
"We came up with a model of human embryos that was developed outside the womb, not the product of sperm and eggs, but the product of human embryonic stem cells that organize themselves into complicated structures," says Brivanlou.
The researchers placed human embryonic stem cells in shells containing a gel and added a protein to persuade the cells themselves to organize three-dimensional hollow spheres that resemble early embryos.
"Our experimental model looks like a sphere – a shell – made of cells, which is what the embryonic tissue looks like at the time," says Mijo Simunovic, lead author of the study.
In addition, the cellular spheres have taken a decisive next step: they have broken the symmetry of the sphere, which begins the development of more complex structures that eventually lead to the development of a human.
"This process of symmetry breaking is an important Holy Grail of developmental biology," says Brivanlou. "Life is a continuation of symmetry-breaking events."
At last being able to recreate that first symmetry-breaking moment and study it now is exciting, humiliating, and "mind-boggling," he says.
"I really feel like one of the best looking A mysterious aspect of our own existence," says Brivanlou.
Brivanlou, Simunovic and their colleagues hope their creations will lead to fundamental discoveries that could have many implications, including a better understanding of the causes of many diseases.
Were very happy about it, "says Simunovic," This is the first time we have been able to achieve this. "
Other scientists agree.
" Scientifically speaking, this research is important, "says Dr. George Daley, a leading stem cell scientist and Dean of Harvard Medical School, "We really have no access to the earliest stages of development. And here we have this remarkable tool in a Petri dish. "
But Daley and Hyun say this kind of research has already raised some questions. " The question is: how long do you create these structures and when do they set? Some of the ethical challenges we have experienced in the history of human embryo biology? "Daley says.
A long-standing policy, known as the 14-day rule, prohibits scientists from using these and more advanced structures in real human embryos to study their labs thoroughly since they have to quit their experiments after 14 days. "The Brivanlou synthetic embryos may eventually approach a true human embryo of 14 days and beyond."
"It certainly indicates that science is on challenging this rule, "says Daley.
" Because the Embry As models become more and more complete and show us how the human body evolves after fertilization, one might wonder: When will these models actually become reality? "Hyun says.
In fact, embryoids have shown early signs of a crucial structure known as primitive streaks. This is another limit to the study of human embryos in the laboratory.
"Research is unpredictable Cells Organize themselves in ways that researchers sometimes find surprising – achieving a level of complexity they did not expect," says Hyun. "Dangers lurk."
For this reason, the International Society for Stem Cell Research plans to revise its guidelines for this type of research, says Daley.
Assessment of the limits of this type of experimentation, "says Daley," Science is so advanced that these guidelines must now re-consider the 14-day rule. "
Rockefeller University scientists agree that researchers and bioethicists must discuss the issues raised by this research, but they insist that the models do not have the same moral status as a human embryo and are far from anything that could ever become a baby.
These are not real human embryos, "says Simunovic," and they would never become human embryos if we let them grow. "
But the researchers plan to develop even more complex embryoids.
" Now we're building this model with complexity to investigate more complex events. "Says Simunovic.