UBC researchers have made a discovery that might lead to eliminating the need for transplant recipients to take drugs to stop their immune systems from attacking a new organ as a foreign object.
The process could also potentially extend the life of transplanted organs so a second and even third transplant is not necessary, a professor of medicine at UBC’s Centre for Blood Research and Life Sciences Institute said.
“It’s exciting work that could have clinical implications for the future,” Jayachandran Kizhakkedathu said on Monday.
“We’re hopeful that this breakthrough will one day improve the quality of life for transplant patients and improve the lifespan of transplanted organs.”
Kizhakkedathu and his team found that by using a special polymer to coat blood vessels on the organ to be transplanted, organ rejection in mice was substantially reduced, results confirmed by collaborators at Simon Fraser and Northwestern University in Illinois.
The title of the peer-reviewed research paper is a mouthful: “Prevention of vascular-allograft rejection by protecting the endothelial glycocalyx with immunosuppressive polymers.” The findings were published on Aug. 9 in Nature Biomedical Engineering.
The drugs that transplant recipients take to prevent immune systems from attacking new organs typically come with serious side effects, Kizhakkedathu said.
This discovery might mean patients wouldn’t need them in the future.
“Blood vessels in our organs are protected with a coating of special types of sugars that suppress the immune system’s reaction, but in the process of procuring organs for transplantation, these sugars are damaged and no longer able to transmit their message,” the doctor said.
So his team synthesized a polymer to mimic those sugars and, working with UBC chemistry professor Stephen Withers, and co-lead authors Daniel Luo, a PhD candidate, and Erika Siren, who has a PhD in chemistry, they developed a chemical process for applying the polymer to blood vessels.
It was Siren’s initial curiosity that led to the discovery, Kizhakkendathu said. She’d been inspired to consider cell-surface engineering after a visit to a B.C. transplant facility.
“I remember seeing an organ sitting in a solution and thinking, ‘Here’s a perfect window to engineer something right,’” Siren said in a statement. “There aren’t a lot of situations where you’ve got this beautiful four-hour window where the organ is outside the body, and you can directly engineer it for therapeutic benefit.”
Jonathan Choy and Winnie Enns of SFU confirmed that a mouse artery, coated in the polymer and then transplanted, displayed strong, long-term resistance to inflammation and rejection.
Caigan Du of UBC and Jenny Zhang of Northwestern University got similar results from a kidney transplant between mice. Megan Levings of UBC and the B.C. Children’s Hospital Research Institute firmed up the findings using new-generation immune cells.
“We were amazed by the ability of this new technology to prevent rejection in our studies,” Choy said. “To be honest, the level of protection was unexpected.”
More than 3,000 Canadians received a transplanted organ in 2019 to avert end-stage organ failure.
The polymer discovery is just a first step, Kizhakkedathu cautioned. So far it has been applied only to blood vessels and kidneys in mice.
Clinical trials in humans could be years away yet.
But he’s hopeful the process will work well on lungs, hearts and other organs.