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The technique that reshapes organ transplantation

At one level, the human liver in the operating room at Chicago’s Northwestern Memorial Hospital was alive. The blood circulating through its tissues supplies oxygen and removes waste products, and the organ produces bile and proteins that are essential for the body.

But the donor had died a day earlier and the liver lay inside a square plastic device. The organ owed its vitality to this machine, which preserved it for transplant to a needy patient.

“It’s a little science fiction,” said Dr. Daniel Borja-Cacho, a transplant surgeon at the hospital.

Surgeons are experimenting with organs from genetically modified animals, hinting that they could be a source of transplants in the future. But the field is already undergoing a paradigm shift, driven by widely used technologies that allow doctors to temporarily store organs outside the body.

Perfusion, as it is called, is changing every aspect of the organ transplant process, from the way surgeons operate to the types of patients who can donate organs and the outcomes for recipients.

Most significantly, surgical programs that have adopted perfusion are transplanting more organs.

Since 2020, Northwestern has seen a 30 percent increase in its liver transplant volume. Nationally, the number of lung, liver and heart transplants each increased by more than 10 percent in 2023, one of the largest year-over-year increases in decades.

Without blood flow, organs deteriorate quickly. That’s why doctors have long considered the ideal organ donor to be someone who died under circumstances that disrupted brain activity but whose heart continued to beat, keeping the organs viable until they could be matched with recipients.

To minimize damage to organs after they were removed from a donor’s blood supply and before connecting them to that of a recipient, surgeons used to cool them to just above the freezing point, which significantly slowed their metabolic processes.

This expands the window in which organs can be transplanted, but only briefly. Livers remain viable for no more than 12 hours, and lungs and heart about six.

Scientists have long experimented with techniques to keep organs in more dynamic conditions, at a warmer temperature and perfused with blood or another oxygenated solution. After years of development, the first device to preserve lungs by perfusion gained approval from the Food and Drug Administration in 2019. Devices to perfuse hearts and livers were approved in late 2021.

Basically, the devices pump blood or an oxygenated liquid through tubes into the blood vessels of the donated organ. Because the cells of a perfused organ continue to function, doctors can better assess whether the organ will thrive in the recipient’s body.

Encouraged by that information, transplant surgeons have begun using organs from older or sicker donors that they otherwise would have rejected, said Dr. Kris Croome, a professor of surgery at the Mayo Clinic in Florida. “We’re looking for organs we never would have had before and we’re seeing good results,” he said.

The infusion also alleviates the grueling process of organ recovery and transplantation, surgeries that last hours and that doctors often perform against the clock, starting in the middle of the night and finishing in consecutive succession.

Now surgical teams can retrieve an organ, perfuse it overnight while they sleep, and complete the transplant in the morning without fear that the delay has damaged the organ.

Perhaps most importantly, perfusion has further opened the door to organ donation by comatose patients whose families have had life support removed, allowing their hearts to eventually stop. Each year, tens of thousands of people die this way, following cessation of circulation, but they were rarely candidates for donors because the dying process deprived their organs of oxygen.

Now, surgeons are perfusing these organs, either by removing them into a machine or, with less technology, by recirculating blood to that region of the donor’s body. And that has made them much more attractive for transplant.

Since 2020, the number of livers transplanted after circulatory death of the donor has doubled, according to an analysis of data from the United Network for Organ Sharing, the nonprofit organization that manages the United States transplant system.

In the past, surgeons never used hearts from such donors because of the organ’s sensitivity to lack of oxygen; In 2023, thanks to perfusion, they transplanted more than 600.

By turning to this new group of donors, transplant centers said they could more quickly find organs for the excess patients in urgent need. Dr. Shimul Shah said the organ transplant program he directs at the University of Cincinnati had virtually eliminated the waiting list for livers. “I never thought, in my career, that I would say that,” he said.

One barrier to technology adoption can be cost. At the rates currently demanded by device manufacturers, perfusing an organ outside the body can add more than $65,000 to the price of a transplant; Smaller hospitals may not be able to justify the initial expense.

One of the leading companies, TransMedics, raised its prices substantially after regulators approved its device, prompting a stern letter from Rep. Paul Gosar, R-Ariz., who wrote: “What began as a promising innovation in medical equipment and an opportunity to increase transplants throughout the country. Now it is being held hostage by a public company that has lost its true north.”

But some surgeons said the technology could nonetheless save money, as patients who receive perfused organs generally leave the hospital faster and with fewer complications, and have better medium- and long-term outcomes.

Surgeons are still exploring the upper limits of how long perfused organs can survive outside the body, and although technologies are already substantially altering transplants, some say this is just the beginning.

Dr. Shaf Keshavjee, a University of Toronto surgeon whose lab was at the forefront of developing technologies to preserve lungs outside the body, said the devices could eventually allow doctors to remove, repair and return lungs to patients. sick instead of replacing them. “I think we can create organs that will survive the recipient you put them in,” he said.

Dr. Ashish Shah, chair of cardiac surgery at Vanderbilt University, one of the most active heart transplant programs in the country, agreed, calling it “the holy grail.”

“Your heart stinks,” he said. “I take it out. I put it on my device. As long as you don’t have a heart, I can support you with an artificial heart for a little while. Then I take your heart and fix it (cells, mitochondria, gene therapy, whatever) and then I sew it back together. Your own heart. “That’s what we’re really working for.”