Successful transplantation of pig hearts into baboons bring human trials a step closer
A newly published study has reported the first successful long-term survival of baboons transplanted with genetically modified pig hearts. The research is a massive leap forward in the ongoing quest to achieve effective cross-species organ transplantation, and more specifically help the many humans that die while on waiting lists for donor organs.
Xenotransplantation, the process of transplanting organs between different species, has long been a goal for many scientists. Human organ donation levels constantly sit below demand, and many people die while waiting for a healthy organ to become available.
Pigs have always been the most promising animal to provide organs for human uses. The animal's organs are generally of a similar size and function to humans, however the big hurdle has been immune rejection from inter-species transplantation.
Since the advent of recent gene editing techniques progress in the field of xenotransplantation has rapidly accelerated. Scientists have been progressively developing genetically engineered pigs that grow organs much less likely to be rejected when transplanted into another species. Baboons have functioned as human surrogates in many transplantation experiments, but until now the longest a baboon has lived after a pig heart transplant has been 57 days.
The latest research represents the passing of a major milestone in the field, with new techniques developed that have resulted in successful pig to baboon heart transplants lasting for between three and six months. One animal was found to maintain good health following the procedure for an impressive 195 days, and in three other instances the experiments were ended due to euthanasia rather than ill health.
The new research presents two key techniques that seem to assist in the success of the procedure. Instead of the regular cold storage system to preserve organs after initial removal, the researchers discovered that organ integrity can be improved by pumping a novel, oxygenated, blood-based solution through the hearts before transplantation into the baboon.
A new drug regime was also developed to reduce organ rejection. The regime comprises a drug that stifles cell proliferation, a modified hormone treatment, and better immunosuppressive medicines. Only one out of the five baboons treated with this new process ultimately died due to transplantation complications.
What this remarkable research suggests is that for the first time in decades scientists may now have a pathway towards successful animal to human organ transplantation. In a commentary piece published in the journal Nature alongside the new research, Christoph Knosalla suggests regulatory bodies need to quickly asses, and reconsider, what specific preclinical results are necessary before human trials can be started.
"Recommendations outlined by the International Society for Heart and Lung Transplantation in 2000 suggest that clinical trials might be considered once 60 percent of primates given life-supporting pig-heart transplants can survive for three months, with at least 10 animals surviving for this time frame, and with some indication that longer survival is possible," writes Knosalla. "The current study goes some way to meeting these criteria."
Jeremy Pearson, from the British Heart Foundation, urges caution in not moving too quickly into human experiments. We may be closer to testing pig hearts in humans, Pearson says, but many questions still need to be resolved.
"To be seriously considered for use in humans," says Pearson, "studies will have to demonstrate greater success than a mechanical pumping device, and ensure that potential safety complications due to viral transmission from the transplanted heart to the recipient can be discounted."
On the viral transmission front, scientists have long been concerned about infection from certain retroviruses that are harmless in pigs but may be fatal to humans. This challenge is already being impressively tackled by researchers using CRISPR gene editing to engineer pig embryos free of endogenous viruses.
So how close are we to testing pig hearts in humans?
There certainly is still some research to be done before that massive leap is made but Bruno Reichart, one of the surgeons working on the new study, suggests it could happen in as little as three years.
The research was published in the journal Nature.