The technique to transform organ transplantation

In a sense, the human liver was alive in the operating room at Northwestern Memorial Hospital in Chicago. The blood circulating through its tissues delivered oxygen and removed waste products, and the organ produced bile and proteins vital to the body.

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

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

Surgeons are experimenting with organs from genetically modified animals, suggesting a future in which they could serve as a source for transplants. But a paradigm shift is already underway in the field, driven by widespread technologies that allow clinicians 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 do it to the types of patients who can donate organs to the outcomes for recipients.

Most importantly, more organs are being transplanted in surgical programs that have introduced perfusion.

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

Without blood circulation, the organs quickly deteriorate. For this reason, clinicians have long viewed the ideal organ donor as someone who died under circumstances that stopped brain activity but whose heart continued to beat, keeping the organs viable until they could be matched to recipients.

To minimize damage to organs after removal from a donor’s blood supply and before joining with that of a recipient, surgeons used to cool them to just above freezing, significantly slowing their metabolic processes.

This extends the window in which organs can be transplanted, but only for a short time. Livers do not remain viable for more than 12 hours, while lungs and hearts only remain viable for up to six hours.

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

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

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

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

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 for comatose patients whose families have withdrawn life support, causing their hearts to eventually stop. Tens of thousands of people die this way every year after circulation stops, but they were rarely considered donor candidates because their organs were deprived of oxygen by the dying process.

Now surgeons perfuse these organs, either by removing them from a machine or, in a simpler way, by circulating blood to that region of the donor’s body. And that has made them much more attractive for a transplant.

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

Once upon a time, surgeons never used hearts from such donors because this organ was sensitive to lack of oxygen. in 2023 they transplanted over 600 thanks to perfusion.

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

One barrier to adopting the technology could be cost. At current prices charged by device manufacturers, perfusion of 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 upfront costs.

One of the leading companies, TransMedics, significantly raised its prices after regulators approved its device, prompting a stern letter from Rep. Paul Gosar, Republican of Arizona, in which he wrote: “What has been described as a promising innovation in medical devices and What began as an opportunity to increase transplant numbers nationwide is now being held hostage by a public company that has lost its true north.”

But some surgeons said the technology could still save money because patients who receive perfused organs generally leave the hospital quicker and with fewer complications achieve better medium and long-term results.

Surgeons are still exploring the upper limits of how long perfused organs can survive outside the body, and as profoundly as technologies are already transforming 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 lungs, repair them and return them to sick patients , rather than replacing them. “I think we can make organs that will survive the recipient you put them in,” he said.

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

“Your heart sucks,” he said. “I’m taking it out. I put it on my device. Even if you don’t have a heart, I can support you with an artificial heart for a short time. Then I take your heart and repair it – cells, mitochondria, gene therapy, whatever – and then I sew it back in place. Your own heart. That’s what we’re really working for.”

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