Organ Perfusion and Cellular Recovery With OrganEx Technology

Cheating on death: Yale scientists restore cells and organ function in pigs after death

Illustration of organ perfusion and cellular recovery using OrganEx technology. The cell-saving blood isotope is delivered to vital organs one hour after death. Credit: Maren Balik

The technology developed by Yale University restores cell and organ function in pigs after death, a potentially breakthrough organ transplant.

Within minutes of the last pulse, a chain of biochemical events resulting from a lack of blood flow, nutrients, and oxygen begins to destroy the body’s cells and organs. However, a team of researchers in

Yale University
Founded in 1701, Yale University is a private research university at the Ivy League in New Haven, Connecticut. It is the third oldest institution of higher education in the United States and is organized into fourteen component schools: the original undergraduate college, the Yale Graduate School of Arts and Sciences and twelve professional schools. It is named after the ruler of the British East India Company Elihu Yale.

“data-gt-translate-attributes=”[{” attribute=””>Yale University has discovered that massive and permanent cellular failure doesn’t have to happen so quickly.

Using a new technology the scientists developed that delivers a specially designed cell-protective fluid to organs and tissues, the team restored blood circulation and other cellular functions in pigs a full hour after their deaths. They report their findings in the August 3 edition of the journal Nature.

Their results may help extend the health of human organs during surgery and expand the availability of donor organs, the authors said.

All cells do not die immediately, there is a more protracted series of events,” said David Andrijevic, associate research scientist in neuroscience at Yale School of Medicine and co-lead author of the study. “It is a process in which you can intervene, stop, and restore some cellular function.”

The research builds upon an earlier Yale-led project that restored circulation and certain cellular functions in the brain of a dead pig with technology dubbed BrainEx. Published in 2019, that study and the new one were led by the lab of Yale’s Nenad Sestan, the Harvey and Kate Cushing Professor of Neuroscience and professor of comparative medicine, genetics, and psychiatry. The new study involved senior author Sestan and colleagues Andrijevic, Zvonimir Vrselja, Taras Lysyy, and Shupei Zhang, all from Yale.

If we were able to restore certain cellular functions in the dead brain, an organ known to be most susceptible to ischemia [inadequate blood supply]We hypothesized that something similar could also be achieved in other implantable vital organs,” Sestan said.

In the new study, scientists applied a modified version of BrainEx called OrganEx to the whole pig. The technology consists of a perfusion device similar to heart-lung machines – which do the work of the heart and lungs during surgery – and an experimental fluid containing compounds that can promote cellular health and suppress inflammation throughout the pig’s body. Cardiac arrest was induced in anesthetized pigs, which were treated with OrganEx an hour after death.

After six hours of treatment with OrganEx, the researchers found that some key cellular functions were active in many areas of the pigs’ bodies – including the heart, liver and kidneys. In addition, some functions of the device have been restored. For example, they found evidence of electrical activity in the heart, which maintains the ability to contract.

We were also able to restore blood circulation throughout the body, which astonished us.”

Usually when the heart stops beating, he said, the organs begin to swell, causing blood vessels to collapse and impair circulation. However, circulation was restored and organs in the deceased pigs that received OrganEx treatment showed their function at the cellular and tissue level.

Under the microscope, it was difficult to tell the difference between a healthy organ and one that had been treated with OrganEx postmortem technology,” Vrselja said.

As in the 2019 experiment, the scientists also discovered that cellular activity was restored in some areas of the brain. However, no structured electrical activity indicating consciousness was detected during any part of the experiment.

The team was particularly surprised to notice involuntary and spontaneous muscle movements in the head and neck regions when they evaluated the treated animals, which remained sedated throughout the six-hour experiment. Sestan said these movements indicate the preservation of some motor function.

The researchers stressed the need for additional studies to understand the apparently restored motor functions in the animals. They also called for a rigorous ethical review from scientists and bioethicists.

Experimental protocols for the latest study were approved by the Institutional Animal Care and Use Committee at Yale University and directed by an external ethical advisory committee.

The researchers said OrganEx technology may eventually have many potential applications. For example, it could extend the life of organs in human patients and expand the availability of donor organs for transplantation. It may also be able to help treat organs or tissues damaged by ischemia during heart attacks or strokes.

“There are many potential applications for this exciting new technology,” said Stephen Latham, director of the Yale Interdisciplinary Center for Bioethics. “However, we need to closely supervise all future studies, particularly those involving brain perfusion.”

Reference: “Cellular Recovery After Prolonged Warm Body Ischemia” By David Andrejevic, Zvonimir Versilia, Taras Lisi, Shube Zhang, Mario Scarica, Anna Spike, David Dellal, Stephanie L. Thorne, Robert B. Decro, Shaoji Ma, Fan Q. Duy, Atagun U. Isiktas, Dan Liang, Mingfeng Li, Suel-Kee Kim, Stefano G. Daniele, Khadija Banu, Sudhir Perincheri, Madhav C. Menon, Anita Huttner, Kevin N. Sheth, Kevin T. Gobeske, Gregory T. Tietjen, Hitten P. Zaveri, Stephen R. Latham, Albert J. Sinusas and Nenad Sestan, 3 Aug 2022, temper nature.
DOI: 10.1038 / s41586-022-05016-1

The research was funded by the US Department of Health and Human Services, the National Institutes of Health, and the National Institute of Mental Health.

This work was supported by the NIH BRAIN Initiative awarding MH117064, MH117064-01S1, R21DK128662, T32GM136651, F30HD106694, and Schmidt Futures.


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