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Newly developed technique restores cell, organ function in post-mortem pigs


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Within minutes of your last heartbeat, a cascade of biochemical events caused by lack of blood flow, oxygen and nutrients begins to destroy your body’s cells and organs. But a team of Yale University scientists found that massive, permanent cell damage doesn’t have to happen so quickly.

Using a new technique they developed to deliver a specially designed cytoprotective fluid to organs and tissues, the researchers restored blood circulation and other cellular functions in pigs an hour after death, said Dr. Reported in the August 3rd edition of the magazine. Nature.

The findings could help improve human organ health during surgery and expand the availability of donor organs, the authors said.

“Not all cells die immediately. There is a longer chain of events,” said David Andrijevic, associate research scientist in neuroscience at Yale Medical School and co-lead author of the study. says. “It’s a process that can intervene, stop, and restore some cellular function.”

The study builds on a previous Yale-led project that used a technology called BrainEx to restore circulation and specific cell functions in the brains of dead pigs. That study and the new one, published in 2019, were led by the lab of Nenad Sestan, Harvey and Kate Cushing Professors of Neuroscience and Professor of Comparative Medicine, Genetics and Psychiatry at Yale University. rice field.

“If we can restore certain cell functions in the dead brain, the organ known to be most susceptible to ischemia, [inadequate blood supply]we hypothesized that something similar could be achieved for other important transplantable organs,” Cestan said.

In a new study involving senior author Sestan and colleagues Andrijevic, Zvonimir Vrsella, Taras Lisi and Shupei Chan, the researchers applied a modified version of BrainEx, called OrganEx, to whole pigs. It consists of a perfusion device, similar to a heart-lung machine that acts as the heart and lungs during surgery, and an experimental fluid containing compounds that promote cellular health and reduce inflammation throughout the pig’s body. One hour after death he induced cardiac arrest in OrganEx-treated anesthetized pigs.

Six hours after treatment with OrganEx, scientists found activation of certain key cellular functions in many areas of the pig’s body, including the heart, liver and kidneys, and restoration of some organ function. discovered. For example, they found evidence of electrical activity in the heart, which retained the ability to contract.

“We were also able to restore circulation throughout the body, which was amazing,” says Sestan.

Normally, when the heart stops beating, organs begin to expand, collapsing blood vessels and disrupting circulation, he said. However, circulation was restored and organs from dead pigs treated with OrganEx appeared to function at the cellular and tissue level.

“Under the microscope, it was difficult to tell the difference between healthy organs and those that had been processed with OrganEx technology after death,” said Vrselja.

Similar to the 2019 experiment, the researchers also found that cellular activity in some areas of the brain was restored, but no organized electrical activity indicative of consciousness was detected in any part of the experiment. .

The team was particularly surprised to observe involuntary and voluntary muscle movements in the head and neck regions when evaluating treated animals that remained anesthetized throughout the 6-hour experiment. The movement shows that some motor functions are being preserved, Sestan said.

The researchers stressed that additional research is needed to understand the animals’ apparently restored motor function, and that rigorous ethical review by other scientists and bioethicists is needed.

Experimental protocols for the latest studies were approved by the Yale University Institutional Animal Care and Use Committee and guided by an external advisory and ethics committee.

The OrganEx technology could eventually have several potential uses, the authors say. For example, it can extend the life of human patient organs and expand the availability of donor organs for transplantation. It may also help treat organs and tissues damaged by ischemia during a heart attack or stroke.

“This exciting new technology has many potential applications,” said Stephen Latham, director of the Yale Interdisciplinary Center for Bioethics. “But all future studies, especially those involving cerebral perfusion, need to be closely monitored.”

Scientists restore some functions in pig brains hours after death

For more information:
Nenad Sestan, Cell recovery after long-term whole-body warm ischemia, Nature (2022). DOI: 10.1038/s41586-022-05016-1.

Courtesy of Yale University

Quote: Newly Developed Technique Restores Cell, Organ Function in Postmortem Pigs (August 3, 2022)

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