A team of Canadian scientists has proven that it is possible to safely convert blood type in donor organs for transplantation. The findings are an important step toward creating universal type O organs, which would significantly improve fairness in organ allocation and reduce patient mortality on waiting lists.
The proof-of-concept study was published in Science Translational Medicine by a team of researchers from UBC, Latner Thoracic Research Laboratories and the University Health Network (UHN) in Toronto.
“With the current matching system, wait times can be significantly longer for patients who need a transplant based on their blood type,” says Dr. Marcelo Cypel, Surgical Director of UHN Ajmera Transplant Center and lead author of the study.
Donor organs are currently matched to potential recipients based on blood type, among other criteria. Blood type is determined by the presence of antigens on the surface of red blood cells and blood vessels in organs – type A blood has antigen A, B has antigen B, blood AB has both antigens and O has none. If the blood type of a donor organ does not match the blood type of the recipient, this can trigger an immune response and the organ is likely to be rejected.
In 2018, UBC researchers, including Dr. Jayachandran Kizhakkedathu, a professor in the Department of Pathology and Laboratory Medicine, discovered a group of enzymes capable of removing antigens from the surface of cells.
For this new study, the enzymes were delivered to the lungs using the Ex Vivo Lung Perfusion (EVLP) circuit, successfully removing the antigens.
“Enzymes are Mother Nature’s catalysts and they perform particular reactions,” said UBC biochemist Dr. Stephen Withers. “This group of enzymes that we found in the human gut can cleave the A and B antigen sugars on red blood cells, converting them into universal type O cells.”
“In this experiment, it opened a gateway to create universal blood-type organs. This is a great partnership with UHN and I was amazed to learn more about the ex vivo infusion system and its impact on transplants. It’s exciting to see our findings translated into clinical research.
Dr. Kizhakkedathu and Dr. Withers went on to found ABOzymes Biomedicala UBC spin-off company working to commercialize enzyme technology.
“There are already upcoming perfusion technologies for the kidneys, so this technology should be transferable to the kidneys, and potentially to other organs,” says Dr. Kizhakkedathu, also a fellow at UBC’s Center for Blood Research.
Addressing wait times for organs
In 2019, 250 Canadians died while waiting for an organ transplant. Type O patients wait on average twice as long to receive a lung transplant as type A patients, says Dr. Aizhou Wang, scientific associate at Latner Thoracic Research Laboratories and first author of the study.
“That translates into mortality. Type O patients who need a lung transplant have a 20% higher risk of dying while waiting for a matching organ to become available,” says Dr. Wang.
This disparity is also present for other organs where a type O or B patient requiring a kidney transplant will be on the waiting list for an average of four to five years, compared to two to three years for types A or AB.
“If you convert all organs to universal type O, you can eliminate this barrier completely,” says Dr. Wang.
This proof-of-concept study was performed at the Latner Chest Research Laboratories. The experiment used the EVLP system developed in Toronto as a processing platform. The EVLP system pumps nourishing fluids through the organs, allowing them to be warmed to body temperature, so they can be repaired and improved prior to transplantation.
Human donor lungs not suitable for transplantation from type A donors were placed in the EVLP circuit. One lung was treated with a group of enzymes to remove antigens from the surface of the organ, while the other lung, from the same donor, remained untreated.
The team then tested each lung by adding type O blood to the circuit, which should trigger an immune response and organ rejection. While the untreated lung showed signs of rejection, the lung treated with the enzymes did not.
“Having universal organs means we could break down the blood-matching barrier and prioritize patients by medical emergency, thereby saving more lives and wasting fewer organs,” adds Dr. Cypel, who is also a professor in the Department of surgery from the University of Toronto and holder of the Canada Research Chair in Lung Transplantation.
The study was an interdisciplinary effort across multiple organizations in Canada, including UHN, University of Toronto, University of British Columbia and University of Alberta.
“By exchanging ideas across disciplines and across the country, we have become a collaborative effort to tackle an important problem in organ transplantation,” says Dr. Wang.
The team of researchers is working on a clinical trial proposal within the next 12 to 18 months.
This story is adapted from a press release about UHN website.