Currently, the supply of donor hearts is not enough to save everyone experiencing terminal heart failure, and many people die waiting for a transplant.
While technology has given some patients with heart failure the power to wait a little longer without a working heart, the only long-term solution for these patients is a heart transplant.
So around the world scientists have been trying to see if animal organs could be used as another option, in a practice known as xenotransplantation.
Researchers have been trying to crack this nut for decades. One of the biggest challenges was just trying to get a primate body to accept a donation from another species – as mammal immune systems go to war on anything they recognise as foreign.
This is where genetic modification comes into play. The pig donors have had their genes modified so their heart tissues don’t express some of the markers that gave away their status as pig tissue, and also to produce other markers that are found in humans.
In a previous experiment using this method, a baboon survived almost three years with a pig’s heart beating alongside its own original heart. But until now, the longest a baboon had survived with a pig heart that’s completely replaced its own, was 57 days.
In this new study, cardiac surgeon Bruno Reichart from Ludwig Maximilian University of Munich and colleagues refined the transplant processes used previously in several ways. And they have achieved far more promising results.
“Porcine hearts are… more vulnerable when compared to human organs,” Reichart explained to ScienceAlert.
“The transplants must be perfused with solutions which carry nutrients and oxygen; the perfusion wasn’t only carried out during storage time but also during implantation.”
Keeping nutrients pumping through the hearts during the whole transplant process proved successful, increasing the recipient baboon’s survival length.
Incidentally, this method may also prove useful in standard human-to-human transplants, according to Christoph Knosalla from German Heart Center Berlin, who wrote an accompanying News & Views piece in Nature about this new study.
If that pans out, it could possibly increase the number of hearts available by allowing the successful transplant of hearts that are not strong enough to withstand the current cold storage techniques.
Another challenge the researchers faced was ensuring that different growth rates of the tissues from the two species didn’t cause problems. In an earlier stage of the experiment the baboons passed away within 40 days due to the pig hearts growing too rapidly once transplanted.
“Pigs (and their hearts) grow within four months to their endpoint of approximately 100 kilograms – in comparison: baboon grow slowly as primates do,” Reichart pointed out. Baboons only reach about 40 kilograms at most.
He explained how including drugs such as temsirolimus into the treatment mix to control the heart’s growth, made sure the heart did not grow too rapidly for the baboon. This drug – also used in cancer treatments – inhibit cells from multiplying, restricting the ability of organ tissues to grow in size.
Reichart and colleagues also reduced the baboon’s blood pressure to the same level in pigs, treated them with temsirolimus to reduce blood clotting and reduced the duration they treated the baboons with steroid cortisone.
Steroid cortisone is used to help suppress the baboon’s immune system, but this type of drug is also known to cause growth in the hearts of babies that have received stem cell transplant, the team noted.
Of the five baboons to receive pig heart transplants using their final refined procedure, four survived for the full three month duration of the experiment (before being euthanised), and a couple of them even went beyond that. The hearts continued beating in good health, keeping the last of the baboons alive for 195 days.
All these modifications seem to have done something right to produce the impressively high survival rate and duration of the healthy, life-supporting transplants.
Although, according to Knosalla, the researchers are yet to work out exactly which modifications were pivotal.
There are still many obstacles to overcome before human testing will even be considered. Reichart told ScienceAlert that next “we need to extend our experience and use a different (humanised) antibody for immunosuppression”.
Another challenge is ensuring the donor animals are safe enough not to infect humans with any cross-species viruses, Reichart explained. Pig viruses such as porcine endogenous retroviruses could pose a risk to recipient humans, although new technologies like CRISPR could help overcome such risks.
International guidelines recommend that human testing shouldn’t happen until at the minimum 10 animals survive for at least three months, and this new research showed that this length of survival is at least possible.
However, by the time these requirements are reached, it’s possible other technologies may make the need for cross-species heart transplants redundant.
Regardless, Reichart and colleagues successfully trialled new techniques that could improve current human-human transplant procedures and showed cross-species heart transplants are a promising option to further explore – for the sake of the millions of people desperately in need of a heart.
This research has been published in Nature.