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Listen: Pig-heart transplants in baboons work for longer than ever before

Improvements to process keep animals with transplanted tickers alive for three times longer.

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Baboons are used as pre-clinical models for transplanting pig hearts, but they don’t live long after a transplant.

Now, improvements to the process have kept baboons alive for three times as long as before1, promising better research in pre-clinical studies of human heart transplants, too. Read the research.

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TRANSCRIPT

Interviewer: Noah Baker

The first human heart transplant was performed in 1967 in Cape Town. This pioneering feat was unfortunately unsuccessful, and the patient died within a few weeks. But as time went on, techniques were improved, outcomes became more favourable. Fast-forward to 1981, and Bruno Reichart carried out Germany’s first successful heart transplant.

Interviewee: Bruno Reichart

That started the renewal of heart transplantation in Germany because everybody thought if such a stupid guy can do it, we can do it as well.

Interviewer: Noah Baker

Bruno went on to do Germany’s first heart-lung transplant, and became the president of the International Federation for Heart and Lung Transplantation.

Interviewee: Bruno Reichart

One of my first patients is still alive I think after 35 or 36 years now.

Interviewer: Noah Baker

Nowadays, more than 5,000 heart transplants are performed every year around the world. But waiting lists are growing and it’s becoming more and more difficult to find donor hearts for those in desperate need.

Interviewee: Bruno Reichart

Well, it’s a story of success. You need more and more organs and the donor pool is the same or if it gets even smaller, especially in Germany, there’s no way in the future that there will be enough hearts to just suffice the needs.

Interviewer: Noah Baker

It’s because of this problem that Bruno became interested in a new type of heart transplant.

Interviewee: Bruno Reichart

I’m involved in the field of xeno-heart transplantation since 1998.

Interviewer: Noah Baker

Xenotransplantation is transplanting an organ from one species into another. In particular, Bruno works with pig hearts and his trials are not using humans, but baboons. Bruno’s hope is than in the future, pig organs could be used for life-saving transplant surgeries.

Interviewee: Bruno Reichart

The heart is only a pump. The muscle contracts, pumps blood. It’s a beautiful, beautiful muscle. No technician can make a machine which lasts for 90 years or so, 80 years. It would just break, fall apart. Nothing will happen when you implant a non-human heart.

Interviewer: Noah Baker

But xenotransplantation is exceedingly complicated. Human immune systems have evolved to reject foreign bodies, and it’s taken decades to overcome these issues for human heart transplantation. Trying to achieve the same when the donor is of a different species, some have said, would be impossible.

Interviewee: Bruno Reichart

It’s actually very difficult and that’s the reason why very smart people say that it’s not possible. The pigs who are on our Earth approximately 90 million years earlier, there’s a difference in the evolution between the animals then and the humans.

Interviewer: Noah Baker

Despite the difficulties, Bruno and his team from Munich have now demonstrated the most successful trials to date — again, not in humans, but in baboons. The transplanted pig hearts kept the baboon subjects alive for more than three times longer than ever before, and this has raised the eyebrows of some others working in the field. Here’s Christoph Knosalla from the German Heart Centre in Berlin, who was not involved in the work.

Interviewee: Christoph Knosalla

I realise that it is really a major step forward in heart xenotransplantation. The group from Munich was able to produce really a sustained survival of more than half a year. Before that, in these life-supporting transplants, the single longest transplant was 57 days.

Interviewer: Noah Baker

In order to achieve this, Bruno and his team pulled together various techniques, some of which have been used by other groups — genetically modifying the pig donors, and applying bespoke immunosuppression protocols to the baboons. They also needed to stop the hearts growing to their full size — pigs are much larger than baboons, and so a full-sized heart would not fit into the chest cavity and would fail.

Additionally, pigs have lower blood pressure than baboons, as they stand on all fours, and so Bruno and his team had to use drugs to thin the baboons’ blood to compensate. And finally, they changed the protocols surrounding the surgery itself. Pig hearts, it seems to Bruno, react differently to human hearts when it comes to transplants.

Interviewee: Bruno Reichart

I think porcine hearts, they look like human hearts, or like primate hearts, but they don’t resist ischemia. Ischemia is a time when the heart is not supplied by oxygen and nutrition, and so they are more vulnerable, and that was a big surprise.

Interviewer: Noah Baker

Bruno used a machine designed by a Swedish group which bathed the donor pig hearts in an oxygenated solution, and before transplant, kept them a bit warmer than in previous attempts at about 8 degrees centigrade. This helped prevent ischemia, which can lead to damage in the heart. Bruno described the surgery.

Interviewee: Bruno Reichart

Then they bring in the porcine heart, and then you do your anastomosis, it’s the left atrium to right atrium, the pulmonary artery, and then you remove the air. It doesn’t bleed because you have done it very meticulously, and you open the clamp and the heart’s getting pink and starts beating. That’s for me amazing.

Interviewer: Noah Baker

The survival of the baboon subjects could be a significant step towards human trials of xenotransplantation, but there’s still a lot of work to be done, and exactly how a human would react is still unclear. Here’s Christoph again.

Interviewee: Christoph Knosalla

Yes, it is not tried in humans. Of course, this is not sure because there are hormone incompatibilities which play a role. So, researchers worldwide, also with other organs, are facing this problem.

Interviewer: Noah Baker

There are also other concerns to overcome, like viruses found in pig DNA, which could possibly be transmitted to humans through transplant. In particular, a family of porcine indigenous retroviruses knows as PERVs. PERVs made the headlines last year, when researchers demonstrated the use of CRISPR to edit PERV genes, but the problem remains to be completely solved. And underlying all of this work, there’s a whole plethora of ethical conversations that need to be had surrounding xenotransplantation.

So, a lot of work to look out for in the future. But the science is progressing, so who knows. Perhaps in the near future, you’ll be listening to this podcast reporting the first successful xenotransplantation, and with it, the next step in medical science.

doi: 10.1038/d41586-018-07653-x
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References

  1. 1.

    Reichart, B. et al. Nature https://doi.org/10.1038/s41586-018-0765-z (2018).

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