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Scientists resuscitate dead cells in pigs, a potential breakthrough for organ transplants

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New research confounds the conventional wisdom about life and death.

Yale University researchers used new technology to restore cells in some organs of pigs that had just died, restoring the animals’ cells to function. The results released on Wednesday in the scientific journal Natureraise profound ethical questions about how medicine defines death but also teases new opportunities for the gathering of people organs for transplantation.

“My eyes widened,” said Brendan Parent, an assistant professor of bioethics at NYU Grossman School of Medicine, of the moment he first read the new results. “My brain went to all the crazy places that we could go in 20 or 30 years.” Parent wasn’t involved with the study but was asked by Nature to write a comment discussing the impact of the new technology .

The research is still in an early, experimental phase and many years away from a possible application in humans. It could ultimately help extend the lives of people whose hearts have stopped beating or who have had a stroke. The technology also shows the potential to dramatically change the way organs are collected for transplantation and increase their availability to patients in need.

When the heart stops beating, blood flow from the body is cut off in a process called ischemia and a cascade of biochemical effects begin. Oxygen and nutrients are cut off from the tissue. cells begin to die. It’s a path to death that causes damage that scientists believe is irreversible.

The new research challenges that idea.

“Cell death can be halted,” said Dr. Nenad Sestan, professor of neuroscience at Yale School of Medicine and author of the new research, during a news conference. “We restored some function to cells in multiple organs that should have been dead.”

The Yale researchers accomplished this feat by constructing a system of pumps, sensors and tubing connected to pig arteries. They also developed a formula containing 13 drugs that can be mixed with blood and then pumped into the animals’ cardiovascular systems. The research builds on that previous work at Yale, which showed that some damage to brain cells may be reversible after blood flow is stopped. Yale has filed a patent for the new technology but is making its methods and protocols freely available for academic or non-profit purposes, the study said.

To assess how well the new system, called OrganEx, worked, the researchers caused heart attacks in anesthetized pigs. The pigs were dead for an hour, and the researchers cooled their bodies and used neural inhibitors to ensure the animals didn’t regain consciousness during subsequent experiments.

Then the researchers began using the OrganEx system. They compared its performance to ECMO, a life support technology used in hospitals today, in which a machine oxygenates blood and circulates it throughout the body.

OrganEx restored circulation and prompted repair of damaged cells. For example, the scientists saw heart cells contract and electrical activity return. Other organs, including the kidneys, also showed improvements, the study said.

The pigs treated with OrganEx startled the researchers. During the experiment, the dead pigs’ heads and necks moved under their own power. The animals remained under heavy anesthesia.

“We can say that the animals were unconscious at those moments, and we don’t have enough information to speculate why they moved,” Sestan said.

The researchers see the neck jerk as an indication that some muscle function has been restored after death.

The OrganEx research is a single study in a laboratory setting where the investigators had complete control over the circumstances of the death and the treatment of the pigs. Nevertheless, the first results open up possibilities that would have seemed like science fiction a few years ago.

“The assumption that depriving the brain or organs of oxygen of oxygen in a matter of seconds to minutes means that those organs are irreparably damaged and lost — that’s not true,” said Nita Farahany, a neuroethicist and law professor at Duke University who was not on the study was involved.

The definition of death is a moving target that has shifted as new life support technologies such as ventilators or ECMO have been developed. Ethicists consider OrganEx to be ECMO on steroids and something that could change the definition of what medical death is.

“Death is a process. Technology has, at several critical moments over the past few decades, shifted the goal posts of when this process begins and when we can say the process of death is complete,” said Parent, the NYU bioethicist. “All iterations of machines that can maintain or restart lung function and/or heart function have changed our perception, our experience of when we can say that saving someone’s life is worthwhile.”

Yale researchers don’t anticipate using OrganEx to treat humans any time soon.

“Before you hook this up to a person to try to reverse whole-body ischemic damage in a human, you would have to do a lot more work. Not that it’s not possible, but there’s still a long way to go,” said Stephen Latham, director of the Yale Interdisciplinary Center for Bioethics. “A lot more experimentation would be needed.”

The impact of even partially reversing the damage in a patient who suffered a fatal heart attack or drowned is immense, he said.

“You would have to think about what condition a person would be restored to if they had been seriously damaged by ischemia and you had given them some sort of perfusate that would have reversed some, but not all, of that damage. That could be a horrible thing, right?” said Latham.

Instead, researchers see more immediate opportunities for real-world use for research. Today, transplant surgeons must strive to stay one step ahead of ischemia and prevent organs from going too long without a blood supply.

OrganEx could help transport transplant organs longer distances and reach people who would otherwise be out of reach for a transplant, Latham said. It could also prevent organ loss from ischemic damage, potentially expanding organ supply.

“From a transplant perspective, when every second counts – what if not? What if we have more time?” Farahany said.

The potential of the new technology raises new and compelling questions in medical ethics – and adds a new twist to some that remain unresolved.

Ethicists have debated the appropriateness of using technologies such as ECMO to preserve organs in patients who have been pronounced dead by cardiorespiratory criteria.

“If we decide someone is dead because their heart stopped, but we use technology to restart their heart—even to preserve organs—does that undermine the determination of death?” Parent asked, sketching the argument over what remains a rare practice.

There’s no regulation for how long doctors must wait to determine death before reusing technology like ECMO to obtain organs for transplantation, Farahany said. OrganEx could allow more time between death and organ preservation.

It’s also possible that OrganEx could change the threshold at which it’s ethical for doctors to let a patient die and then save their organs for donation.

“In the short term, it’s not a treatment. But if it’s that effective, it could be a treatment — you certainly couldn’t recover someone’s organs if you could keep doing things to save their life,” Farahany said.

It’s a technology that’s still in its infancy, but could be powerful enough to redefine the line between life and death.

https://www.nbcnews.com/science/science-news/scientists-reanimate-dead-cells-pigs-potential-breakthrough-organ-tran-rcna41014 Scientists resuscitate dead cells in pigs, a potential breakthrough for organ transplants

Fry Electronics Team

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