April 12, 2024

The technology that is revolutionizing organ transplantation

At one level, the human liver was alive in the operating room at Northwestern Memorial Hospital in Chicago. The blood circulating through the tissues provided oxygen and removed waste products, and the organ produced bile and proteins essential to the body.

But the donor had died a day earlier and the liver was in a boxy plastic device. The organ owed its vitality to this machine, which preserved it for transplantation into a needy patient.

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

Surgeons are experimenting with organs from genetically modified animals, hinting at a future where they could be a source for transplants. 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, to the outcomes for recipients.

Most importantly, surgical programs that use perfusion transplant more organs.

Since 2020, Northwestern has seen a 30 percent increase in liver transplants. Nationally, the number of lung, liver and heart transplants will each increase by more than 10 percent by 2023, one of the largest annual increases in decades.

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

To minimize injury to organs after removing them from a donor’s blood supply and before connecting them to that of a recipient, surgeons cooled them to just above freezing, significantly slowing their metabolic processes.

This extends the period in which organs can be transplanted, but only briefly. Livers remain viable for no more than twelve hours, and lungs and hearts closer to six hours.

Scientists have long experimented with techniques to keep organs in more dynamic conditions, at a warmer temperature and perfused with blood or another oxygen-rich solution. After years of development, the first lung perfusion preservation device received Food and Drug Administration approval in 2019. Devices for perfusing hearts and livers were approved in late 2021.

The devices essentially pump blood or an oxygen-rich fluid through tubes into the blood vessels of the donated organ. Because cells in a perfused organ continue to function, doctors can better judge whether the organ will thrive in the recipient’s body.

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

Perfusion also eases the grueling process of organ recovery and transplantation, hours-long operations that doctors often perform against the clock, starting in the middle of the night and completed one after the other.

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

Perhaps most importantly, perfusion has further opened the door to organ donation by comatose patients whose families have withdrawn life support, eventually causing their hearts to stop. Tens of thousands of people die this way every year after circulation is stopped, but they were rarely donor candidates because the dying process deprived their organs of oxygen.

Now surgeons perfuse these organs, either by placing them in a machine or, in a less technical way, by circulating blood in that part of the donor’s body. And that has made them much more attractive for transplantation.

Since 2020, the number of livers transplanted into the circulation after the 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 transplant system in the United States.

Once upon a time, surgeons never used hearts from such donors because of that organ’s sensitivity to oxygen deprivation; in 2023 they have transplanted more than 600 thanks to perfusion.

By tapping into this new cadre of donors, transplant centers said they could more quickly find organs for surplus patients in urgent need. Dr. Shimul Shah said the organ transplant program he heads at the University of Cincinnati has essentially wiped out the waiting list for livers. “I never thought in my career that I would ever say that,” he said.

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

One of the leading companies, TransMedics, significantly raised its prices after regulators approved the device, prompting a stern letter from Rep. Paul Gosar, Republican of Arizona, who wrote: “What started as a promising innovation in the field of medical equipment and an opportunity to increase the number of transplants across the country is now being held hostage by a publicly traded company that has lost its true north.”

But some surgeons said the technology could still save money because patients who receive perfused organs typically 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 vascularized organs can survive outside the body, and as substantially as technologies are changing transplantation, some say this is just the beginning.

Dr. Shaf Keshavjee, a surgeon at the University of Toronto whose lab has been 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 sick patients instead of replacing them. “I think we can make organs that survive the recipient you put them in,” he said.

Dr. Ashish Shah, chairman of cardiac surgery at Vanderbilt University, one of the nation’s busiest heart transplant programs, agreed, calling it “the holy grail.”

“Your heart sucks,” he said. “I’ll take it out. I put it on my device. Even if you don’t have a heart, I can support you for a while with an artificial heart. I then take your heart and fix it – cells, mitochondria, gene therapy, whatever – and then I sew it back in. Your own heart. That is what we are really committed to.”

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