The successful transplantation test marks a major step toward more compatible, accessible organ donations.
Special enzymes developed at UBC have enabled the first successful test of a human kidney transplant converted from blood type A to universal type O, helping to prevent a mismatch and rejection of the organ.
The achievement, outlined today in Nature Biomedical Engineering, marks a major step toward helping thousands of patients get kidney transplants sooner.
For the first-in-human experiment, an enzyme-converted kidney was transplanted into a brain-dead recipient with consent from the family, allowing researchers to observe the body’s immune response for the first time.
For two days, the kidney functioned without signs of hyperacute rejection, the rapid immune reaction that can destroy an incompatible organ within minutes. By the third day, some blood-type markers reappeared, triggering a mild reaction, but the damage was far less severe than in a typical mismatch, and researchers saw signs that the body was beginning to tolerate the organ.
The breakthrough is the result of more than a decade of work to develop the organ-converting enzymes by UBC Medicine professor Dr. Jayachandran Kizhakkedathu and UBC Science professor Dr. Stephen Withers.
“This is the first time we’ve seen this play out in a human model,” said Dr. Withers, a professor emeritus in the UBC department of chemistry. “It gives us invaluable insight into how to improve long-term outcomes.”
The journey to universal donor organs
In the early 2010s, Dr. Withers and Dr. Kizhakkedathu, a professor in the UBC department of pathology and laboratory medicine and the Centre for Blood Research, were focused on making universal donor blood by stripping away the sugars that define blood types.
Those same sugars, or antigens, coat organ blood vessels. If a recipient’s immune system detects the wrong antigen, it attacks. Type-O patients can only receive type-O organs, however, type-O kidneys are often given to others because they’re universally compatible. As a result, type-O patients typically wait two to four years longer, make up more than half of people on kidney waitlists, and many die waiting.
Traditional methods for overcoming blood-type incompatibility in transplants require days of intensive treatment to strip antibodies and suppress a recipient’s immune system—and require organs from living donors. The new approach changes the organ rather than the patient, meaning transplants could be performed faster, with fewer complications, and for the first time could unlock the use of blood-type mismatched organs from deceased donors—when every hour can determine whether a patient lives or dies.
The key to this approach is the 2019 discovery by the UBC team of two highly efficient enzymes that remove the sugar that defines type-A blood, effectively converting it to type O.
“These enzymes are highly active, highly selective, and work at very low concentrations,” said Dr. Kizhakkedathu. “That made the whole concept feasible.”
The next challenge was applying this to whole organs, achieved in 2022 when a Toronto team showed lungs could be converted. After successful tests outside the body with blood, then lungs and kidneys (with the University of Cambridge), the question remained: Could an enzyme-converted organ survive inside a human immune system?
The answer came in late 2023 on an overseas trip for Dr. Kizhakkedathu.
“Our collaborators showed me their data where, using our enzymes, they had converted a human kidney and transplanted it into a brain-dead recipient. It was working beautifully.” He stayed up late to call Dr. Withers first thing in the B.C. morning. “I was so thrilled. It was a dream moment.”
Blood-type antigens act like nametags on cells, and the UBC enzymes act as molecular scissors, snipping off the ‘nametag’ that marks type A and revealing type O beneath.
“It’s like removing the red paint from a car and uncovering the neutral primer,” said Dr. Withers. “Once that’s done, the immune system no longer sees the organ as foreign.”
Regulatory approval for clinical trials is the next hurdle, and UBC spin-off company Avivo Biomedical will lead development of these enzymes for transplant application and to enable the creation of universal donor blood on demand for transfusion medicine.
The potential is enormous. “This is what it looks like when years of basic science finally connect to patient care,” said Dr. Withers. “Seeing our discoveries edge closer to real-world impact is what keeps us pushing forward.”
A version of this story was originally published on UBC News.