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Doctors changed the blood type of human lungs in the lab, opening the door to life-saving universal organs

Business Insider US
Lungs are hooked up to a perfusion machine at Dr. Marcelo Cypel's lab in Toronto, Canada.
  • Doctors converted human lungs from Type A blood to Type O — the universal donor — for the first time.
  • It's a step toward universal organ transplants, so patients don't die because donor organs aren't a blood-type match.
  • But converted organs eventually reverted to Type A — an issue animal and clinical trials will study.
  • For more stories visit www.BusinessInsider.co.za

For the first time, doctors changed the blood type of human lungs — an experimental step toward creating universal organs that could be transplanted into any patient, regardless of blood type.

An average 17 people die each day waiting for a life-saving organ, according to the Health Resources and Services Administration. Many don't receive a heart, lung, or kidney because the available organs are the wrong blood type for them. At the same time, organs can go to waste because no recipient of the same blood type is available — a tragedy when life-saving organs are so scarce.

Dr. Marcelo Cypel, a lung-transplant surgeon at the Ajmera Transplant Centre in Canada, often gets donor lungs that don't match his most critical patients. He's found himself performing transplants on less urgent patients, whose blood types matched available organs, while others died because they couldn't obtain matching organs in time.

Transplant surgeons face a similar issue in the US, where 42% of the population has Type A blood, according to the Stanford Blood Center. People with Type O or Type B blood often have to wait longer for transplants, since they can't receive Type A organs, because their bodies would attack them as foreign objects.

Bags with blood donations in Nairobi, Kenya, on February 14, 2022.

Type O blood is the "universal donor," since it can be given to people of any blood type without their bodies rejecting it. (Type O can only receive their own blood type.)

In a cutting-edge attempt to eliminate blood-type criteria, Cypel led a cohort of researchers to convert three human lungs from Type A to Type O blood, possibly transforming them into universal organs. Their findings were published in the journal Science Translational Medicine on Wednesday.

While experimental, if the technique works in human transplant trials, it could save lives by making organs available to more of the 106,000 people on the US national organ-transplant waiting list.

A major hurdle to overcome 

Spiny mice at the Bursa Metropolitan Municipality Zoo in Bursa, Turkey, on November 29, 2018.

Still, a major issue could limit this discovery to the lab: Eventually, converted organs revert back to their original blood type. After that happens, a patient's body might reject the transplant, leaving them without a functional organ and possibly killing them.

Cypel's team plans to run trials in mice to see how long it takes their new organs to revert and how the mice respond.

Dr. Alyssa Burgart, a transplant anesthesiologist and bioethicist at Stanford University, who was not involved in the study, told Insider she was cautious about the new research.

"There are a lot of hurdles left before you would be able to utilise one of these organs in a transplant recipient," she said, adding, "I would want to see it successfully utilized in an animal model before putting a patient through that risk."

Still, Cypel thinks his team could start transplanting converted organs into human patients in about a year, if the mouse studies go well. It's too early to say how many people would be involved in these clinical trials, but Cypel said proof-of-concept studies usually have about 10 patients. If that goes well, they can progress to larger trials and other organs.

"I think that will change, a lot, the landscape of organ transplantation," Cypel said, adding, "There is no reason to think that that wouldn't work for kidneys and hearts and liver."

An enzyme scrubs Type A blood, helping it evade antibody attacks

Dr. Aizhou Wang demonstrates injecting enzymes into the perfusion system at Dr. Marcelo Cypel's lab in Toronto, Canada.

Cypel was inspired when, in 2019, researchers led by biochemist Stephen Withers used an enzyme to remove the antigens, or signature sugar molecules, from Type A blood. That effectively turned the blood into Type O, which doesn't have antigens for the immune system to attack. (That's why anybody can receive Type O blood or organs.)

Cypel reached out to Withers and together they designed an experiment to test whether the enzyme could do the same for organs.

They took three pairs of lungs from deceased donors, for a total of six lungs, and flushed three of the lungs with the enzyme, using a machine that pumps fluid through the organs to keep them alive, at the University Health Network's Ajmera Transplant Centre, where Cypel is the surgical director.

Each donor set had one lung treated with the enzyme, and one untreated lung. After four hours, the enzyme had scrubbed 97% of A antigens in the blood vessels of the treated lungs.

Then Cypel's team pumped all the lungs full of Type O plasma — the antibody-carrying element of blood. Within an hour, the plasma showed signs of rejecting the untreated lungs, deploying antibodies that inflamed the organ tissue. The lungs that had been flushed with the enzyme sustained no such injury over six hours of observation.

A long journey to real-world application

Doctors perform a kidney transplant.

Organs reverting to an incompatible blood type inside a patient's body is a significant hurdle for the researchers to overcome. But Cypel is optimistic. If they can evade the immune response that usually attacks an incompatible organ immediately after transplant — by scrubbing the A antigens out of the organ — they could prevent the body from rejecting the organ once it develops A antigens again, Cypel thinks.

"That's still somewhat a speculation at this moment," he added.

According to Dr. Si Pham, a transplant surgeon at the Mayo Clinic in Florida, who was not associated with the new research, the antigen-scrubbing technique could help new lungs survive the critical two weeks after transplant surgery. That's when the body often launches its most vicious attack against an organ it won't accept.

While antibodies could still attack the organ once it reverts to its original blood type, there are ways to prevent that, Pham said. Patients could take extra immunosuppressing medications (though that comes with its own danger of infection and illness), or doctors could periodically inject the antigen-scrubbing enzyme into the patient's veins, assuming it's proven safe.

Even in the best-case scenario, it could be a decade, or longer, before the technology is available to patients. Clinical trials alone would involve years of monitoring patients after their converted-organ transplant. The first benchmark would be one year after transplant, then five years. Cypel hopes they can start clinical trials with kidneys at around the same time as they test their converted lungs.

At the same time, Withers's research group is looking beyond Type A blood and searching for an enzyme that can convert Type B blood to Type O. In theory, that could allow them to make Type B organs universal as well.

"It's a step towards helping us to get more organs to more patients," Pham told Insider, adding, "This is the first step."

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