Scientists have long been attempting to find a solution to the shortage of donor organs. The national waiting list for organ donors grow every ten minutes. Yet everyday, most of the people in that list die without getting the organ transplant that they need.
What if we can grow these organs instead of waiting for a donor to harvest them from?
4-week old pig embryo injected with human cells before its development stages. (c) Juan Carlos Izpisua Belmonte
The Salk Institute and its team of researchers have taken a huge step toward answering that question and making that idea more than just a possibility.
“In ancient civilizations, chimeras were associated with God,” says Jun Wu, a Salk Institute scientist and the paper’s first author. He follows up with the idea our ancestors introduced that “the chimeric form can guard humans.” And their team hopes to see a future when human-animal hybrids can do exactly that.
The most commonly known process of making a chimera is to introduce the cells or organs of one animal to another. But as is the case with a lot of organ transplants, this presents a huge risk when the host’s immune system decides to reject the introduced organ.
So the Salk Institute team went with another approach: beginning at the embryonic level. By this process, the host cells and the introduced cells can grow together during the embryo’s development.
It took the team a total of four years and forty collaborators to finally figure out how to make a human-animal chimera.
Learning From What They Already Know
Prior chimera research, particularly those conducted on mice and rats, were huge stepping stones in the team’s success. Though, not without great difficulty.
Their trial and error process included injecting stem cells from rats into pig blastocysts--which failed due to the differences in gestation times and evolutionary ancestors of the two species. Pigs and humans, however, have remarkably similar organs.
Even so, the different gestation times of pigs and humans presented another challenge: getting the timing just right. “We tried three different types of human cells, essentially representing three different times” in the developmental process, explains Wu.
Through their experiments, they discovered that pig embryos can only survive when injected with human stem cells that have already developed a bit more. These embryos were then put into adult pigs, which carried those embryos for up to four weeks before they were removed again to be analyzed.
Still A Ways To Go
The team managed to create a total of 186 later-stage chimeric embryos that survived, says Wu, and they estimated that each had about one in 100,000 human cells.
The low percentage could present a problem in the long run, says Ke Cheng, a stem cell expert at the University of North Carolina at Chapel Hill and North Carolina State University. The human tissue slows the growth of the embryo even more, which increases the risk of organs coming from these embryos being rejected by humans.
Cheng says they need to figure out how to introduce more human cells into the pig embryos, or if that would even be possible. Juan Carlos Izpisua Belmonte, a professor in the Salk Institute’s Gene Expression Laboratory, agrees and says that it could take years before the current process can actually be used to grow functioning organs for humans.
However, both Cheng and Belmonte both believe that what has been achieved is a great breakthrough. And the insights these scientists are gaining from seeing how this process works, discovering how it can be further developed, is just as valuable as eventually finding success.