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

New research confounds conventional wisdom about life and death.

Researchers at Yale University used a new technology to restore cells in certain organs of pigs that had just died, bringing the animals’ cells back to life. The findings, published Wednesday in the scientific journal Nature, raise deep ethical questions about how medicine defines death, but also tease new possibilities for harvesting human organs for transplant.

“My eyes were wide open,” said Brendan Parent, an assistant professor of bioethics at the NYU Grossman School of Medicine, of the moment he first read the new findings. “My brain went to all the crazy places we could go in 20 or 30 years.” The parent was not involved in the study, but was asked by Nature to write a commentary discussing the implications of the new technology.

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

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

New research challenges this idea.

“Cell death can be stopped,” Dr. Nenad Sestan, professor of neuroscience at Yale School of Medicine and author of the new research, said during a press conference. “We restored certain cell functions in many organs that should have been dead.”

The Yale researchers accomplished this feat by building a system of pumps, sensors and tubes connected to pig arteries. They also developed a formula of 13 medicinal drugs that can be mixed with blood and then pumped into the animals’ cardiovascular system. The research builds on previous work at Yale, which showed that some damage to brain cells could be reversible after blood flow is cut off. Yale has filed a patent for the new technology, but is making its methods and protocols freely available for academic or nonprofit use, the study says.

To assess how well the new system, called OrganEx, works, the researchers induced heart attacks in anesthetized pigs. The pigs were dead for an hour, and the researchers cooled their bodies and used nerve blockers to ensure the animals would not regain consciousness during subsequent experiments.

The researchers then 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 caused damaged cells to repair. For example, scientists saw heart cells contract and electrical activity return. Other organs, including the kidneys, also showed improvements, the study says.

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

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

Researchers believe that the neck jerk is an indication that some muscle function was restored after death.

The OrganEx research is a single study in a laboratory setting in which the researchers had complete control over the conditions of death and treatment of the pigs. Even so, the early results open up possibilities that would have seemed like science fiction a few years ago.

“The assumption that the loss of oxygen to the brain or organs within 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 involved. in the study. .

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

“Death is a process. “Technology, at several critical moments over the last few decades, has changed the goals of when that process begins and when we can say that the dying process is over,” said Parent, the NYU bioethicist. “All the 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 it’s worth trying to save someone’s life.”

The Yale researchers don’t foresee using OrganEx to treat humans anytime soon.

“Before you can plug this into a person to try to reverse whole-body ischemic damage in a human, you’re going to need to do a lot more work. Not that it couldn’t be done, but that would be a long way off,” said Stephen Latham, director of Yale’s Interdisciplinary Center for Bioethics. “There’s a lot more experimentation that will be required.”

The implications of only partially reversing the damage in a patient who has suffered a fatal heart attack or who has drowned are enormous, he said.

“You’d have to think about what a person would be restored to if they were severely damaged by ischemia and you gave them some kind of perfusion that reversed some but not all of that damage. That could be a terrible thing, right?” Latham said.

Instead, researchers see more direct avenues to real-world use for the research. Today, transplant surgeons must fight to stay ahead of ischemia and prevent organs from going too long without a blood supply.

OrganEx could help transplant organs move 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 injury, potentially extending the organ supply.

“From a transplant perspective, when every second is critical — what if it’s not? What if we have more time?’ Farahani said.

The possibilities of new technology open up new and exciting questions of medical ethics — and add a new twist to some that remain unresolved.

Ethicists have debated whether it is appropriate to use technology such as ECMO to preserve organs in patients who are pronounced dead by cardiorespiratory criteria.

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

There is no regulation on how long doctors must wait to determine death before restarting technology like ECMO to preserve organs for transplant, Farahany said. OrganEx could allow more time between death and organ preservation.

It’s also possible that OrganEx could change the boundary of when it’s ethical for doctors to let a patient die and then keep their organs for donation.

“In the long run, it’s not a cure. But if it’s that effective, it could be a cure — you certainly couldn’t get organs back from somebody if you could keep doing things to save their life,” Farahany said.

It’s a technology that remains in its early stages, but could be impactful enough to redefine the line between life and death.

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