Innovative coating for blood vessels reduces rejection of transplanted organs

An international team led by researchers from UBC and SFU have developed a promising new biotechnology that could reduce and even eradicate the need for life-long immunosuppressants for organ transplant recipients.

Until now, the success of transplants has largely rested on the efficacy of immune suppressing drugs that are given systemically, which counter the body’s rejection of a foreign object, but have serious side effects throughout the body. 

Jayachandran Kizhakkedathu, a professor in the Department of Pathology and Laboratory Medicine at UBC, and his team have developed a polymer that prevents the immune system from rejecting a transplanted organ. The polymer can be confined to the blood vessels in a transplanted organ, with no systemic impacts.

SFU’s team, led by Molecular Biology and Biochemistry professor Jonathan Choy, tested the efficacy of this new protective coating with positive results. The collaborative research is published today in the journal Nature Biomedical Engineering.

 “Blood vessels in our organs are protected with a coating of a special type of sugars that direct the immune system’s reaction, but in the process of procuring organs for transplantation, this protective coating on the blood vessels is damaged, which triggers rejection of the transplant,” explains Kizhakkedathu.

Working with PhD candidates Erika Siren and Daniel Luo at the Centre for Blood Research and Chemistry and UBC Chemistry Professor Stephen Withers, the team was able to synthesize the sugars and developed chemistry to “paint” the blood vessels of the new organ with a new polymer-based protective coating during organ storage prior to transplant.

The new coating camouflages the damage created when the new organ is procured which, in turn, stops the body from triggering an immune response. “The coating allowed us to fortify  the organ’s local immunosuppressive properties, which can potentially reduce the amount of post-implant immunosuppressants needed for patients,” Kizhakkedathu says.

Siren had just started her PhD with Kizhakkedathu when she started thinking about how cell surface engineering—the modification of cell surfaces to enhance its functionality—could apply to her research.

“I remember visiting a lab at B.C. Transplant and seeing an organ sitting in a solution and thinking, here’s a perfect window to engineer something right. 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,” she says.

Once the team ascertained that their polymer did support immunosuppressing capabilities, they turned to Choy’s lab at SFU. 

With the help of microsurgeon Winnie Enns at SFU, Choy was able to paint the new coating on mouse arteries before implanting them in a new host body. Arteries that are transplanted from one mouse to another are normally rejected, but rejection was substantially diminished when the arteries were coated with the polymer.

“We were amazed by the ability of this new technology to prevent rejection in our studies. To be honest, the level of protection was unexpected,” Choy says.

Kizhakkedathu and Choy are hopeful that this breakthrough will improve quality of life for transplant patients by reducing their reliance on immunosuppressive drugs, and improve the lifespan of transplanted organs, which typically last for about five years.  The researchers recognize that clinical trials in humans could be several years away.

 “Additional studies using clinically relevant animal models with a similar immunological landscape to humans are needed in order to assess the full magnitude of this cell surface engineering approach,” Kizhakkedathu says.

“We also need to better understand how this technology is inhibiting the immune system in order to translate the findings appropriately,” Choy adds.

The researchers are optimistic that the procedure could work equally well on lungs, hearts and other organs—good news to the country’s prospective organ donor recipients. In 2019, more than 3,000 Canadians underwent organ transplantation with the aim of averting end-stage organ failure.

The research was supported by CIHR, NSERC, UBC, SFU, the Heart and Stroke Foundation of Canada, GlycoNet and the Michael Smith Foundation for Health Research.