Intestinal enzymes open a gateway to create donor organs of universal blood group

Research published in Scientific translation medicine Performed at the Latner Thoracic Surgery Research Laboratories and UHN’s Ajmera Transplant Center, it has been demonstrated that blood types can be safely converted in donor organs intended for transplantation. This finding is an important step in creating universal type O organs, significantly improving the fairness of organ allocation and reducing the mortality rate of patients on the waiting list.

Current matching systems can significantly increase the waiting time for patients requiring a transplant, depending on their blood type. “

Dr. Marcelo Sipel, Surgical Director of Azimera Transplant Center and Senior Author of Research

“Having a universal organ means that we can remove blood matching barriers, prioritize patients by medical urgency, save more lives and waste fewer organs. “Masu,” adds Dr. Cypel, who is also a thoracic surgeon at UHN’s Splot Surgery. Chairman of the Canadian Research Committee for Surgery and Lung Transplantation at the University of Toronto.

Blood type is antigen On the surface of red blood cells-; Type A blood has A antigen, B has B antigen, AB blood has both antigens, and O has no antigen. If the antigen is foreign to our body, it can provoke an immune response. Therefore, for blood transfusions, you can only receive blood from donors of the same blood type as us, or universal type O.

Similarly, antigens A and B are present on the surface of blood vessels in the body, including those of solid organs. For example, if a person of type O (meaning that there are anti-A and anti-B antibodies in the bloodstream) receives an organ from a type A donor, that organ is probably rejected. As a result, the donor organ is matched against potential recipients of the waiting list based on blood type, among other criteria.

Patients with type O take an average of twice as long to receive a lung transplant as patients with type A, says Dr. Aizhou Wang, a science associate in Dr. Cypel’s lab and lead author of the study. I will explain.

“This leads to mortality. Patients with type O who need a lung transplant have a 20% increased risk of dying while waiting for a matching organ to become available,” said Dr. Wang. I am.

This disparity is also found in other organs, with type O or B patients requiring kidney transplants on an average 4-5 year waiting list compared to type A or type 2-3 years. increase. AB.

“Converting all organs to Universal Type O can completely remove that barrier.”

experiment

This proof-of-concept study was conducted at Dr. Cypel’s laboratory, which is part of the Laterer Thoracic Surgery Research Laboratories.In the experiment ExAlive The pulmonary perfusion (EVLP) system pioneered in Toronto as a therapeutic platform. The EVLP system pumps nutrients through the organs and warms them to body temperature, allowing them to be repaired and improved prior to transplantation.

Human donor lungs unsuitable for transplantation from Type A donors were placed in the EVLP circuit. One lung was treated with a group of enzymes to remove the antigen from the surface of the organ, while the other lung from the same donor remained untreated.

The team then added type O blood (including high levels of anti-A antibody) to the circuit to test each lung and simulate an ABO-incompatible transplant. The results showed that the treated lungs were well tolerated and the untreated lungs showed signs of rejection.

Intestinal enzymes are the key to creating universal organs

This study was successful thanks to important interdisciplinary efforts across multiple Canadian organizations, including UHN, the University of Toronto, the University of British Columbia, and the University of Alberta.

“By exchanging ideas across disciplines and across the country, it has become one collaborative effort to address key issues in organ transplantation,” said Dr. Wang.

Dr. Stephen Wizards, a UBC biochemist, and his team discovered a group of enzymes in 2018. This was the key to this first step in creating a universal blood group organ. These enzymes were delivered to the lungs in this study using the EVLP circuit.

“Enzymes are Mother Nature’s catalysts and carry out specific reactions. This group of enzymes found in the human intestine cuts sugars from the A and B antigens of red blood cells and converts them into universal type O cells. can.

“In this experiment, this opened a gateway for creating organs of universal blood type,” explains Dr. Wizards.

“This is a great partnership with UHN and I ex vivo Impact on the perfusion system and its transplantation. It’s exciting to see our findings reflected in clinical research, “adds Dr. Wizards.

As a next step, the team of researchers is working on clinical trial proposals within the next 12-18 months.