The world's first hybrid embryos, including genetic material from both pigs and humans, have been created by a team of International scientists.
"The ultimate goal is to grow functional and transplantable tissue or organs, but we are far away from that," says lead investigator Juan Carlos Izpisua Belmonte, a professor in the Salk Institute of Biological Studies' Gene Expression Laboratory. "This is an important first step."
Other uses include insights into early human development and disease onset, and providing a realistic drug-testing platform. But for now, however, they are helping scientists understand how human stem cells grow and specialise.
But why pigs?
Not only are pigs and humans about five times more distant evolutionarily than mice and rats, but pigs also have a gestation period that is about one-third as long as humans, so the researchers needed to introduce human cells with perfect timing to match the developmental stage of the pig.
"It's as if the human cells were entering a freeway going faster than the normal freeway," says Izpisua Belmonte. "If you have different speeds, you will have accidents."
The researchers injected several different forms of human stem cells into pig embryos to see which would survive best. The cells that survived longest and showed the most potential to continue to develop were "intermediate" human pluripotent stem cells.
So-called "naive" cells resemble cells from an earlier developmental origin with unrestricted developmental potential; "primed" cells have developed further, but are still capable of giving rise to several different cell types. "Intermediate cells are somewhere in between," says Wu.
The human cells survived and formed a human/pig chimera embryo. That's a real thing that exists now. Welcome to the future.
Embryos were implanted in sows and allowed to develop for between three and four weeks. "This is long enough for us to try to understand how the human and pig cells mix together early on without raising ethical concerns about mature chimeric animals," says Izpisua Belmonte.
Even using the most well-performing human stem cells, the level of contribution to the chimerized embryo was not high. "It's low," says Wu.
Izpisua Belmonte considers this good news. One concern with the creation of human/animal chimeras is that the chimera will be too human. For instance, researchers don't want human cells to contribute to the formation of the brain.
In this study, the human cells did not become precursors of brain cells that can grow into the central nervous system. Rather, they were developing into muscle cells and precursors of other organs.
"At this point, we wanted to know whether human cells can contribute at all to address the 'yes or no' question," he says. "Now that we know the answer is yes, our next challenge is to improve efficiency and guide the human cells into forming a particular organ in pigs."
To do this, the researchers are editing the pig genome, as they did with mice, to open gaps that human cells can fill in. The work is in progress.
The project was funded by the Fundacion Seneca in Murcia, Spain, the Universidad Catolica San Antonio de Murcia, the Fundacion Dr. Pedro Guillen, the G. Harold and Leila Y. Mathers Charitable Foundation, and The Moxie Foundation.