- The Washington Times - Sunday, September 15, 2019

Scientists have developed a device that can produce dozens of synthetic human embryo-like parts simultaneously, calling it a tool that could improve the understanding of early human development.

“By making such embryo-like structures from human stem cells, we have now available to us reliable experimental platforms to study human development without using human embryos,” said Jianping Fu, one of the study’s researchers and an associate professor of mechanical engineering at the University of Michigan.

Using devices that can manipulate fluids, the team of researchers were able to build embryo-like structures that resemble the core of an implanting human embryo, according to their article published last week in the journal Nature.

They created models of the amniotic ectoderm (which develops into the membrane that encloses a developing fetus) and the epiblast (which develops into all the cell types found in the human body) from human stem cells.

But the researchers excluded some important cell types from the embryo-like parts such as the trophoblast, which develops into the placenta, Mr. Fu said.

“These embryo-like structures will be very powerful for advancing human embryology and reproductive biology. These embryo-like structures will also be useful for drug and toxicity screens to prevent pregnancy failure and birth defects,” Mr. Fu said, adding that the team created them in controllable, reproducible and scalable ways.

The researchers made 12 to 15 embryo-like structures simultaneously at a 95% success rate, he said. Mr. Fu estimates that since 2016 the team has produced a few hundred embryo-like parts, keeping them less than four days.

The research has raised some ethical concerns about the idea of “synthetic” or “artificial” embryos, and Mr. Fu said he understands why some people might feel uncomfortable with the concept.

“We are well aware of the sensitivity of our research,” he said.

But he stressed that what he and the team have created are a mass of cells that mimic portions of a developing embryo that cannot develop into a fetus. He said the research team has no intention of creating a “synthetic embryo” and has “no scientific reason” to do so.

Josephine Johnston, director of research and research scholar at the Hastings Center, a bioethics research institute, said the team’s study could raise the question of whether the embryo-like structures can be manipulated to create a fetus or whether these scientific techniques are bringing society closer to creating embryos from stem cells, which she described as likely implausible but understandable concerns for the public.

Ms. Johnston also questioned if the word “embryo” is the correct terminology for Mr. Fu’s team’s work if the structures cannot develop in the womb, cautioning about language use to describe scientific models.

She said the stem cell work, along with cloning research and in vitro fertilization, raise similar concerns about the prospect of embryos having no family structure, and growing them inside people’s bodies and the manipulation of human life. Ms. Johnston added that religious concerns also play a role, which is why there is opposition to in vitro fertilization.

“Anytime you are modeling human biology, you are only creating a model. So it’s never quite the same, and it can’t necessarily answer all the same questions,” she said of Mr. Fu’s team’s study and the growth of cultured cells in a dish. “But it is often a really important intermediary step before moving into doing experiments with humans.”

The Fu team’s work is the first demonstration of a bona fide human embryo-like structure and shows that such structures can be made from pluripotent or induced pluripotent stem cells in vitro, according to Anna-Katerina Hadjantonakis, a developmental biologist for the Sloan Kettering Institute.

“What’s important is that this method is very robust and reproducible. Many identical structures can be generated at once, all having similar morphology which approximates to the human embryo,” she said. “The work opens the door and provides an accessible method for future studies in other laboratories.”

Mr. Fu said he and the team are interested in continuing to “polish” the stem cell in vitro system using fluid-controlling devices to prolong the culture of human embryo-like structures.

He said other scientists have been able to create structures that resemble complete mouse embryos and implant those synthetic embryos into a surrogate. However, there has been no further development of artificial animal embryos beyond early implantation, he said.

Mr. Fu said he and his group created a 3D culture system using human stem cells two years ago. Other scientists have reported building 3D systems using mouse and human stem cells.

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