Technology developed by Yale restores cell and organ function in pigs after death

Technology developed by Yale restores cell and organ function in pigs after death

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

Using a new technology the team developed that delivers a specially formulated cell-protecting fluid to organs and tissues, the researchers restored blood circulation and other cellular functions in pigs a full hour after they died, they report in the journal’s dated issue August 3 Nature.

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

Not all cells die immediately, there is a more protracted series of events,” said David Andrijevic, associate researcher in neuroscience at Yale School of Medicine and co-lead author of the study. “It’s a process that you can intervene in, stop, and restore some cellular function.”

Illustration of organ perfusion and cell recovery using OrganEx technology.
Illustration of organ perfusion and cell recovery using OrganEx technology. The cell-sparing blood analog is delivered to vital organs one hour after death. (Image credit: Marin Balaic)

The research builds on an earlier Yale-led project that used technology called BrainEx to restore blood flow and certain cellular functions to the brain of a dead pig. This and the new study were published in 2019 and 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.

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 be achieved with other vital transplantable organs as well,” Sestan said.

In the new study – which involved lead author Sestan and colleagues Andrijevic, Zvonimir Vrselja, Taras Lysyy and Shupei Zhang, all from Yale – the researchers 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 treated with OrganEx one hour after death.

Six hours after treatment with OrganEx, the scientists found that certain key cellular functions were active in many areas of the pig’s body – including the heart, liver and kidneys – and that some organ functions had been restored. For example, they found evidence of electrical activity in the heart that maintained the ability to contract.

We were also able to restore blood flow throughout the body, which amazed us,” Sestan said.

Normally, when the heart stops beating, organs begin to swell, blood vessels collapse and block circulation, he said. Nevertheless, blood flow was restored and the organs of the deceased pigs that received OrganEx treatment appeared to be functional at the cellular and tissue level.

Under the microscope, it was difficult to see the difference between a healthy organ and an organ treated with OrganEx technology after death,” Vrselja said.

As in the 2019 experiment, the researchers also found that cellular activity was restored in some areas of the brain, although no organized electrical activity that would indicate consciousness was detected during part of the experiment.

The team was particularly surprised to observe involuntary and spontaneous muscle movements in the head and neck when evaluating the treated animals, which remained anesthetized throughout the six-hour experiment. Those movements indicate preservation of some motor functions, Sestan said.

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

The experimental protocols for the latest study were approved by Yale’s Institutional Animal Care and Use Committee and governed by an external advisory and ethics committee.

Finally, the OrganEx technology could have several potential applications, the authors said. For example, it could extend the lifespan of organs in human patients and expand the availability of donor organs for transplantation. It could also help treat organs or tissues damaged by ischemia from heart attacks or strokes.

There are numerous potential applications of this exciting new technology,” said Stephen Latham, director of the Yale Interdisciplinary Center for Bioethics. “However, we must carefully monitor any future studies, particularly those involving brain perfusion.”

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

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

The study was conducted at the Yale Translational Research Imaging Center, co-authored by Dr. Albert Sinusas, Professor of Medicine, Radiology and Biomedical Engineering. The Nature paper contains a full list of authors.

Leave a Comment

Your email address will not be published.