How scientists revived dead pig organs and what the feat means for transplants

Using a special machine that pumps blood and other bodily fluids throughout the body, researchers allowed the cells and organs of pigs to recover one hour after they died from cardiac arrest. This feat has the potential to one day increase the number of human organs available for transplantation.

The team connected the animal’s circulatory system to OrganEx, a system that pumps a mixture of blood and fluid-borne nutrient “perfusate” around the body.Cells from all major organs in anesthetized and euthanized pigs not only survived but also showed signs of cell repair, the team wrote last week. Nature.

This system was adapted from an earlier model called BrainEx. In 2019, researchers demonstrated that the latter can be used restore circulation in pig brain after animal death. The latest version of his OrganEx perfused the organ more effectively than other cardiopulmonary bypass devices known as ECMO (extracorporeal membrane oxygenation) machines that have been tested in pigs, the team wrote. In the new study, pigs were compared to his three control groups of animals measured at different time points after death.

None of the animals showed coordinated brain activity indicative of consciousness after the system was activated. Still, the experiment raises ethical questions about the definition and meaning of death.

Scientific American We spoke with study co-authors Zvonimir Vrselja and David Andrijevic, a physician and neuroscientist at the Yale School of Medicine, about how OrganEx works, development challenges, and ethical considerations.

[An edited transcript of the interview follows.]

Why did you develop the OrganEx system and how did you build the previous BrainEx system?

VRSELJA: When our first study was published in 2019, the main takeaway was that things don’t die as quickly as we assumed. After that, I had many interactions with my colleagues. The idea was whether this would work in the brain. The brain is the most complex and sensitive organ. [circulatory death], should also work in all other organs.Therefore, we decided to test the whole body 1 hour after ischemia. [after blood flow stops]and can basically replicate the cell-sparing findings of the original study.

So is there any idea that organs from recently deceased people could one day be kept alive and stored for long periods of time before being transplanted?

VRSELJA: Think about the organ shortage. We have a big waiting list. For example, kidneys are the most needed organ. And now, if this system is optimized so that it can accept people who have been dead for an hour and whose organs are not suitable for transplantation, ideally, [can] Maybe start using those organs. After all, it’s not science because there is science. You want to do something because it’s important.

ANDRIJEVIC: You want to save people’s lives.

Can you explain how OrganEx works?

ANDRIJEVIC: Basically, the whole technology consists of two key components. We call it “his ECMO on steroids” because there are many different pumps and sensors, artificial kidneys in the system, etc.

Another critical part of this technique is the perfusate. [the liquid that is pumped throughout the body], based on the original BrainEx perfusate. But now it is compatible with the whole body and, as shown in the paper, optimized to work in other vital organs such as the kidneys, heart and liver. There is an immune system, a coagulation system, and an autonomic nervous system. Therefore, this perfusate is optimized to control those things as well. The animal’s vasculature is connected to the system for mechanical control of organ perfusion. Internally, the circulating fluid is actually a one-to-one mixture of the animal’s endogenous blood and perfusate.

Why wasn’t the animal’s blood used alone rather than combined with the perfusate?

VRSELJA: It doesn’t work.

ANDRIJEVIC: That’s right. One of our control groups was ECMO, a clinical standard that only attempted to restore circulation using the animal’s own blood. And it was terrible.

Blood is a living tissue. Wait an hour and the living tissue (the cells inside) will begin to die. The dead material in the blood cannot restore circulation. Our perfusate is completely acellular and contains no cells at all.

Your system pumps out a mixture of blood and perfusate. Isn’t the animal’s heart beating at that point?

ANDRIJEVIC: We observed restoration of electrical ventricular activity in the heart, as reported in the paper. I also visually observed that the heart was actually contracting. However, the quality of these heartbeats is controversial and we have not evaluated them in a proper way.

How did your system keep the pig’s cells from dying after they were euthanized by electric shock?

VRSELJA: When cells are shocked [such as when blood stops pumping]they die first.

ANDRIJEVIC: Then you can actually reach these organs with the perfusate once you restore the circulation. there is hope “

Do you think your system will be used in humans with life-threatening organ failure in the future?

VRSELJA: That’s a difficult question to answer. Because now we are aiming at organ recovery.

ANDRIJEVIC: Before we even think about translating this technology, we need a lot of animal testing to see how well this works, etc.

How did the OrganEx experiment address ethical considerations?

ANDRIJEVIC: We were really careful. All our experiments are planned and supervised by both Yale Universities. [Institutional Animal Care and Use] Committees and External Advisory [and ethics] Committee. Throughout the experiment, animals were chilled and neuroleptics were reduced in the perfusate to reduce their brain activity. [brain activity]We also added anesthesia throughout the experiment.

Foresee the point where you would say these experiments have gone too far?

VRSELJA: We’re working on cell recovery, and we’ve always taken a ground-up approach. And for these things to happen, the cells have to be alive. But with all the work that has been done in recent years regarding bioethics and the development of guidelines and approaches, there is clearly a social commitment and interest in this. I think it depends on the wider community of scientists and ethicists.

Ultimately, we want to make sure that the underlying problem of organ shortages is addressed and addressed in the best possible way.