Using only skin cells, Israeli lab makes synthetic mouse embryos with beating hearts

An Israeli lab has grown synthetic mouse embryos with brains and beating hearts — in an egg-free sperm-free procedure that used stem cells taken from skin.

The breakthrough, published on Monday in the peer-reviewed journal Cell, represents the first time that an advanced embryo of any species has been created from stem cells alone, cell biologist Prof. Jacob Hanna of the Weizmann Institute of Science told The Times of Israel.

Hanna, whose team of researchers includes Jews and Arab Israelis as well as a Palestinian doctoral student, said that previous attempts had led only to blastocysts, meaning the structures formed in the early development of mammals. Blastocysts have a tiny fraction of the million-plus cells that are in his embryos.

“It’s amazing,” he commented. “There was no sperm, no egg and no uterus, but we managed to get embryos formed from stem cells alone to eight days — a third of the gestation period of a mouse — with a beating heart.”

He said that the research could one day be used to grow artificial human embryo-like structures to generate cells for futuristic medical solutions.

Scientists are constantly working on ways to use cells to grow organs for transplant. The obvious source for such cells—regular embryos—is seen as rife with ethical problems.

A synthetic mouse embryo grown at Weizmann Institute of Science, pictured dally, from day one top left, to stay eight bottom right. (courtesy of the Weizmann Institute of Science)

Hanna said synthetic embryo-like structures could be viewed very differently. They are similar to regular embryos, but are not viable for implantation.

He foresees a day when sick patients may give skin or blood cells for the growth of artificial embryo-like structures, which could in turn yield the cells needed to grow organs.

A synthetic mouse embryo grown at Weizmann Institute of Science on day eight, complete with a beating heart. (courtesy, the Weizmann Institute of Science)

The key to Hanna’s achievement is a special incubator system in which each embryo is in a bottle with liquid, and the bottle is spinning to ensure it does not attach to the side. The incubator creates all the necessary conditions for the embryo’s development, including gas concentration, pressure and temperature. The liquid — developed in his lab — gives the embryos all the nutrients, hormones, and sugars they need.

Dr. Jacob Hanna at his Weizmann Institute lab. (courtesy, Jacob Hanna)

In March 2021, Hanna’s lab used the incubator to grow 250-cell embryos into mouse fetuses with fully formed organs using artificial wombs. “The difference between that research and what we achieved now is where the embryos come from,” Hanna explained. “In the previous study, they were natural embryos that came from mice and originated as eggs fertilized by sperm. Now, the embryos are made purely from stem cells.”

He added: “We were asking at the time of the previous study what would happen if we took just stem cells and put them in this machine. Now we know the answer — embryos with early-form organs, including an early brain, a beating heart, blood stem cells. They even mimic the whole embryo, and the tissues around it include the placenta and the yolk sack.”

“Nobody has made advanced embryos from stem cells, ever, so this is significant. This will advance both understanding of stem cells and organs in mammals, and is likely to have practical significance in the future.”

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