Not your type? Perhaps not a problem.
A kidney that had been converted from blood type A to type O was transplanted into a human body for the first time, with help from UBC research.
Transplantation is the best treatment for those with late-stage kidney disease, but if the donated organ isn’t compatible with the recipient’s blood type, their immune system may reject the new organ. Waiting for compatible organs can take years, especially for type O recipients; type O organs can be given to type A or B recipients, but type O recipients can only receive type O organs, making their pool of compatible organs even smaller.
ABO-incompatible transplantation is a way of widening access to the supply — organs less dense in antigens (sugars on blood cells that indicate ABO type) can be transplanted if the recipient’s blood type antibodies are removed through an external machine, a process called plasmapheresis. However, the preparation required for the recipient can take days, and is only practical with a living donor because there’s less time to prepare the recipient when transplanting organs from deceased donors.
Transplants using blood type-converted kidneys, as explored in the recently-published Nature Biomedical Engineering study, don’t rely on time in the same way. “Our approach opens it up completely because it’s donor-centric,” said Dr. Stephen Withers, professor emeritus in the department of chemistry and corresponding author on the study. “[The] treatment can be done in an hour, and you don’t need to have any treatment of the recipient ahead of time.”
Withers and his team identified an enzyme pair in 2019 that could remove antigens from blood cells, allowing them to convert A-type cells into O-type cells.
For blood cells, once the antigens are removed, the ABO type is permanently changed. However, with organs, the antigens regenerate.
This is part of why Withers initially thought the enzyme discovery wouldn’t be useful to organ transplantation. However, transplant surgeons had shed some light on the situation: even if the antigens came back, the initial lack of antigens could help avoid hyperacute rejection. This type of rejection happens in the first hour or so, when antibodies in the blood bind to the surface of the transplanted organ and initiate the process of organ-death.
“If you can avoid that early phase by removing those antigens, then when these antigens really reappear … we should be able to control that,” Withers said.
In this study, the donor kidney was pre-treated with these enzymes. The researchers ensured that the converted organs could be viable in two different temperatures — 37°C, a temperature used to maximize enzyme production, and 4°C, a temperature organs are generally kept at before transplantation. They first modelled incompatible kidney transplants with a machine that simulates body conditions, which showed that enzyme-treated kidneys held up better in antibody-rich blood than non-treated kidneys.
With ethical approval from the recipient’s family and from ethics committees, the researchers transplanted an enzyme-treated kidney into a brain-dead recipient in China who hadn’t received antibody preparation. They monitored the recipient for several days afterward.
No hyperacute rejection took place. Antigen regeneration then began, and antibody-mediated rejection was diagnosed on day four post-operation. This became more severe in the days after, but fared better than non-enzyme-treated, hyperacutely-rejected kidneys.
Some damage to the kidney could be related to the physical process of monitoring it — 40 biopsies were performed over the monitoring period. “In an actual [transplant], you wouldn’t be doing any of that stuff, and you [would] be using all the immunosuppressives,” said Withers.
Nevertheless, the experiment is the first demonstration of immune compatibility for enzyme-converted donor organs in a human recipient, making it a step toward more effective incompatible transplantation. Before clinical trials, more decedent experiments — studies using brain-dead recipients — will likely take place to further this process, according to Withers, but with immunosuppression methods.
One barrier to getting this donor-centric model through regulatory approval is money. “It’s expensive and not easily fundable. You’re not going to be able to write a grant to do that sort of thing, typically,” said Withers. This kind of work is also not suited to graduate students because it’s tedious and repetitive.
“The only real solution to move this forward … was to form a company so that we could raise money to do the work and to hire technical people who could perform the experiments.”
This was how Avivo Biomedical came to be. Based at UBC, the company is dedicated to reducing barriers caused by blood type incompatibility. Withers is a co-founder and serves on the board of directors.
The enzyme conversion process also lends itself to other organs like hearts and lungs, which require the donor to be deceased before transplantation. Withers said preparations are already underway for transplantation of other organs in brain-dead recipients.
“Our colleagues in Toronto have permission to go ahead and do decedent studies … We’re just basically waiting for the right situation to arrive.”
Withers emphasized that developing this study was a long process, full of reassessing what they were doing to get where they wanted to go. He explained the key to this work was not only collaboration and patience, but years of building up the fundamental knowledge.
“[It’s] being prepared to learn the basics, because it came out of the basics.”
First online
Share this article
Submit a complaint Report a correction
