All-inclusive organs: Lungs successfully converted to universal blood type

Lungs donated for transplants can now be converted to a universal blood type, making the organs compatible with any patient, as shown in a recent study. This medical feat is expected to dramatically improve organ allocation in transplants worldwide.

“Donor organ allocation is dependent on ABO blood group system matching, [among other criteria], restricting the opportunity for some patients to receive a life-saving transplant,” according to a team of Canadian researchers from the University Health Network (UHN), Ontario, Canada, who developed the procedure for universal blood-type organ conversion.

Blood type is established by the presence of antigens on the surface of red blood cells (RBCs)—type A blood has the A antigen, B has the B antigen, AB has both antigens, and O has none, they said. Antigens A and B can also be found on the surfaces of blood vessels in the body, including vessels in solid organs.

A patient with blood type O, for example, cannot receive an organ from a type A donor, because the organ would be rejected. Meanwhile, a patient with blood type A can receive organs from donors with the same blood type as them, type AB, or the universal type O.

Deleting antigens with enzymes

In a bid to shorten wait times for organ transplants, the team conducted a series of experiments to clear any antigens from the surface of lungs using the combination of two enzymes, FpGalNAc deacetylase and FpGalactosaminidase. Found in the human gut, these enzymes have been reported to effectively convert group A red blood cells to group O in a separate work by researchers from the University of British Columbia (UBC) in Canada. [BCMJ 2018;60:411-414]

In the first experiment, the UHN team tested the ability of the enzymes to remove the A antigen from five human A1 RBC samples and three human aortae after static incubation. At concentrations as low as 1 μg/ml, the enzymes were able to remove about 99 percent and 90 percent of A antigens from RBCs and aortae, respectively. [Sci Transl Med 2022;doi:10.1126/scitranslmed.abm7190]

Next, the researchers performed the experiment using eight A1 human lungs. Baseline analysis showed that A antigens were predominantly expressed in the endothelial and epithelial cells of the lungs. Delivery of the enzymes during ex vivo lung perfusion (EVLP) led to the removal of more than 97 percent of endothelial A-Ag within 4 hours. There was no treatment-related acute lung toxicity documented.

The last experiment was an ABO-incompatible lung transplant simulation. One set of lungs was treated with a group of enzymes to clear the A antigens, while the other set remained untreated (control). Afterwards, the researchers added type O blood (with high concentrations of anti-A antibodies) to each of the lungs during EVLP.

Results showed that compared with untreated lungs, treated lungs had minimal antibody binding, complement deposition, and antibody-mediated injury. In other words, the untreated lungs showed signs of rejection, whereas the treated lungs were tolerated well.  

More lives saved, less organs wasted

The group of enzymes used to create universal blood-type organs can cut sugars from the A and B antigens on red blood cells, converting them into universal type O cells, as pointed out by UBC biochemist Dr Stephen Withers who, along with his team, identified the enzymes in 2018.

“This is a great partnership with UHN, and I was amazed to learn about the ex vivo perfusion system and its impact for transplants. It is exciting to see our findings being translated to clinical research,” Withers said.

“Having universal organs means we could eliminate the blood-matching barrier and prioritize patients by medical urgency, saving more lives and wasting less organs,” added Dr Marcelo Cypel, Surgical Director of UHN’s Ajmera Transplant Centre and the senior author of the current study.

Not having to wait long to receive a lung transplant, for one, can translate to improved survival outcomes, specifically for patients with blood type O, who have a 20-percent higher risk of dying while waiting for a matched organ to become available as compared with those who are type A, explained Dr Aizhou Wang, scientific associate at Cypel's lab and first author of the study.

Such disparity is also present for other organs, Wang added, where a patient with blood type O or B and in need of a kidney transplant will be on the waitlist for an average of 4–5 years as compared to 2–3 years for those who are type A or AB.

Cypel and Wang shared that they are already working on a proposal for a clinical trial within the next 12 to 18 months.