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San Diego Lab Creates Partially Human Pig Embryos

Credit: Juan Carlos Izpisua Belmonte/Cell Press

Above: Pigs at a facility in Spain that collaborated on experiments to create partially human embryos are seen in this undated photo.

The human elements of the pig embryos were limited, but experts say this study represents a significant first step toward the goal of one day growing human organs in animals.

In a new study published Thursday, researchers at the Salk Institute in La Jolla report using stem cells to create pig embryos partially made up of human cells. The human elements of the embryos were limited, but experts say this study represents a significant first step toward the goal of one day growing human organs in animals.

Scripps Research Institute stem cell scientist Jeanne Loring said via email that researchers will need to continue exploring the basic science involved in creating human-animal "chimeras" for some time. But she said, "The advances reported here make me confident that a solution will be found and human organs will eventually be made routinely in animals."

Video by Katie Schoolov

The study's first author Jun Wu — a scientist in Juan Carlos Izpisua Belmonte's lab at the Salk Institute — says the ultimate goal is to be able to take cells from a human patient, reprogram them into stem cells and strategically incorporate them into an animal embryo, thus creating an animal with a humanized organ genetically suited for transplantation back into the patient.

The results described in Cell are far from realizing that dream. Chimeric embryos were successfully implanted into pigs, and the researchers did see human cells in some embryos turning into the early stages of developing organ tissue.

But the success rate of these experiments was much lower than what the researchers achieved in another set of experiments involving rat organs grown in mice. Those mice were able to live a normal lifespan with rat organs such as the pancreas, heart and eyes.

Wu says despite the challenges ahead, he and colleagues have shown an important proof of concept.

"We see the human cells become the precursors of the cardiomyocytes — the heart — and also the liver, the pancreas and the gut," said Wu. "So the potential is there."

Credit: Juan Carlos Izpisua Belmonte/Cell Press

The mouse chimera in this undated image shows properties of a rat, including its dark brown coat.

Creating human-animal chimeras is seen by some as a promising way to meet demand for transplantable organs. Twenty-two people die each day waiting for an organ transplant, according to the U.S. Department of Health & Human Services.

However, this research has also been the subject of ethical debate. The National Institutes of Health has even imposed a ban on funding for such research. To carry out this study, the Salk researchers relied on donations from private foundations and collaborated with scientists and pig farmers in Spain as well as UC Davis.

One ethical concern centers around the possibility of incorporating human cells into an animal's brain. That could raise questions about whether such an animal would exhibit human sentience, making it off limits for experimentation. Wu says one promising finding in this study was that human cells did not incorporate into the central nervous system of these early-stage pig embryos.

"We have those concerns too," said Wu. "That's why in this study we chose to stop the pregnancy at three to four weeks."

Wu says at this point, he and his colleagues aren't aiming to bring a human-pig embryo to term. They first want to establish better ways to coax human stem cells into becoming useful embryonic organ tissue, and to prevent them from becoming brain cells.

Beyond the potential for developing transplantable organs, the researchers also say their work shows that chimeras may be useful for studying evolution.

They were surprised to find rat gallbladders growing in their mouse chimeras, because rats themselves don't develop gallbladders. The researchers say the rat genes that were coded for the gallbladder inside the mouse may provide clues about how rats have evolved to no longer require this organ.

UC San Diego sociology professor John Evans says ethical concerns could be raised if cross-species mixing were taken many steps further, but this study didn't cross the line.

"Of course, people with a strong animal rights view would think all of this is unethical," Evans said. But, he said, "I think most people would not strongly object to this sort of experimentation. Unless at some point in the future you start creating pigs that have human-like traits. But I don't think this research comes anywhere close to that."

UC San Diego stem cell scientist Alysson Muotri said via email that he was impressed with the paper's efforts to lay the groundwork for new ways of potentially helping patients in the future.

"This manuscript is a good first step towards the identification of the best procedures for a future production of human organs in large animals," Muotri wrote.

Photo by Katie Schoolov

Salk scientist Jun Wu stands with other members of the Belmonte lab at the Salk Institute, Jan. 25, 2017.

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