The pigs had already been dead for an hour, and yet, the cells of their hearts, brains and livers were still kicking.
Thanks to a new system called OrganEx, scientists can now keep the dying organs of recently deceased pigs alive by hooking the animals up to a system of pumps, filters and flowing fluids. This procedure does not restore the animals' brain function or pull the pigs back from the great beyond; rather, it ensures that certain cellular functions in the animals' vital organs keep going.
In the future, the system could potentially be used to help preserve and restore donated human organs destined for use in transplantation procedures, scientists reported in a new study, published Wednesday (August 3) in the journal Nature. This process could expand the number of organs available for transplant by reversing the effects of ischemia — in which an organ suffers damage from inadequate blood flow and oxygen supply — in donated organs.
And in theory, such a device could also be used in living humans to treat ischemia that occurs during a stroke or heart attack, Dr. Robert Porte, a professor in the department of surgery at the University of Groningen in the Netherlands who was not involved in the study, wrote in an accompanying commentary of the work.
However, the technology won't be applied to living humans or donated organs anytime soon.
"This is very far away from use in humans," Stephen Latham, director of the Yale Interdisciplinary Center for Bioethics and co-author of the study, told reporters in a news briefing on Tuesday (Aug. 2). The proof-of-concept experiment in pigs demonstrated that the OrganEx system can restore some cellular functions in some organs after blood stopped flowing to those organs, but the degree of recovery differed between organs.
"We'd need to study [in] a lot more detail the degree to which ischemic damage is undone in different kinds of organs before we'd be even close to trying an experiment like this on a human being who had suffered anoxic damage," meaning organ damage from a lack of oxygen, Latham said.
The team plans to study OrganEx in many more animal studies "before even thinking about translating" the technology to humans, Dr. David Andrijevic, an associate research scientist in neuroscience at the Yale School of Medicine and co-first author of the study, said at the briefing.
How OrganEx works
The new research builds upon a previous study, published in 2019 in the journal Nature, in which the researchers used a smaller version of the same system to restore some cellular and metabolic activity in the brain of a pig that had been decapitated during food production.
This smaller system, called BrainEx, pumped a liquid chock-full of Hemopure — a synthetic form of the protein hemoglobin, which carries oxygen in red blood cells — through the brain's blood vessels. The liquid also contained chemical compounds intended to prevent blood clots from forming and cells from self-destructing through a process called "apoptosis." Pumping this fluid through the brain prevented the organ from swelling, as it usually would after death, and allowed certain cellular functions to continue up to four hours post-decapitation. (Importantly, the treated brain did not produce any electrical signals associated with normal brain function or "remnant awareness," the authors confirmed.)
"Cells actually don't die as quickly as we assume that they do, which basically opens up a possibility for intervention," Dr. Zvonimir Vrselja, an associate research scientist in neuroscience at the Yale School of Medicine and co-first author of the study, said at Tuesday's press briefing. In other words, if scientists can step in soon enough, they can save some cells from certain doom.
In their latest work, the team essentially scaled up their BrainEx system to perfuse a whole pig body at once.
The scaled-up system uses a device similar to a heart-lung machine, which takes over the role of the heart and lungs during surgeries by pumping blood and oxygen through the body. The team used this device to pump both pig blood and a modified version of their synthetic, cell-saving liquid through the deceased pigs' bodies. Their synthetic solution contained 13 compounds intended to suppress inflammation, stop blood clot formation, prevent cell death and correct electrolyte imbalances that arise when ischemia sets in.
To test OrganEx, the team induced cardiac arrest in anesthetized pigs, and then after an hour, they connected the animals to the device. They compared the OrganEx-treated pigs to pigs treated with an extracorporeal membrane oxygenation system (ECMO), which only pumped oxygenated blood through the animals' bodies.
After six hours, the team found that ECMO didn't sufficiently perfuse all the animals' organs with blood and many blood vessels had collapsed, as they typically would after death; the ECMO-treated animals also showed extensive signs of hemorrhage and tissue swelling. By comparison, OrganEx reduced the degree of cell death and improved the preservation of tissues throughout the body.
What's more, OrganEx-treated pigs showed signs of cellular repair unfolding in the brain, heart, lungs, liver, kidney and pancreas, and these vital organs retained certain cellular and metabolic functions over the six-hour experiment. The heart, in particular, showed signs of electrical activity and was able to contract. Further examination of the pigs' hearts, kidneys and livers also revealed that specific genes involved in cellular repair had been activated in the organs, whereas they hadn't in the ECMO-treated pigs.
"What this tells us is that the demise of cells can be halted and their functionality restored in multiple vital organs, even one hour after death," Dr. Nenad Sestan, a professor of neuroscience at the Yale School of Medicine and the study's senior author, said at the briefing.
The results hint that, someday, OrganEx or components of the system could be applied in the treatment of ischemia and in the preservation of transplant organs, particularly in the case of "donation after circulatory death," in which donated organs have been deprived of blood circulation for some time prior to transplant, Porte wrote in his commentary. But again, much more research is needed before the system can be applied in either setting.
In follow-up work, the research team wants to better understand how, where and to what extent OrganEx restores cellular function in different animal organs. In addition, they'll need to evaluate whether and how their synthetic solution needs to be adapted for use in human tissues. And ethical and practical concerns must be addressed before even considering using the system in living humans, Latham said at the briefing.
"You have to think about, 'What is the state to which a human being would be restored if they had been seriously damaged by ischemia and you gave them a perfusate that reversed some, but not all, of that damage?'" he said. "The salvaging of organs, and the maintenance of organs for transplant, is I think a much closer and much more realistic clinical goal that could be based on this study."
Originally published on Live Science.
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Nicoletta Lanese is the health channel editor at Live Science and was previously a news editor and staff writer at the site. She holds a graduate certificate in science communication from UC Santa Cruz and degrees in neuroscience and dance from the University of Florida. Her work has appeared in The Scientist, Science News, the Mercury News, Mongabay and Stanford Medicine Magazine, among other outlets. Based in NYC, she also remains heavily involved in dance and performs in local choreographers' work.