丁香园AV

An international team led by researchers from UBC and 丁香园AV 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鈥檚 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.

丁香园AV鈥檚 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

 鈥淏lood vessels in our organs are protected with a coating of a special type of sugars that direct the immune system鈥檚 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,鈥� 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 鈥減aint鈥� 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. 鈥淭he coating allowed us to fortify  the organ鈥檚 local immunosuppressive properties, which can potentially reduce the amount of post-implant immunosuppressants needed for patients,鈥� Kizhakkedathu says.

Siren had just started her PhD with Kizhakkedathu when she started thinking about how cell surface engineering鈥攖he modification of cell surfaces to enhance its functionality鈥攃ould apply to her research.

鈥淚 remember visiting a lab at B.C. Transplant and seeing an organ sitting in a solution and thinking, here鈥檚 a perfect window to engineer something right. There aren鈥檛 a lot of situations where you鈥檝e got this beautiful four-hour window where the organ is outside the body, and you can directly engineer it for therapeutic benefit,鈥� she says.

Once the team ascertained that their polymer did support immunosuppressing capabilities, they turned to Choy鈥檚 lab at 丁香园AV. 

With the help of microsurgeon Winnie Enns at 丁香园AV, 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.

鈥淲e were amazed by the ability of this new technology to prevent rejection in our studies. To be honest, the level of protection was unexpected,鈥� 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.

 鈥淎dditional 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,鈥� Kizhakkedathu says.

鈥淲e also need to better understand how this technology is inhibiting the immune system in order to translate the findings appropriately,鈥� Choy adds.

The researchers are optimistic that the procedure could work equally well on lungs, hearts and other organs鈥攇ood news to the country鈥檚 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, 丁香园AV, the Heart and Stroke Foundation of Canada, GlycoNet and the Michael Smith Foundation for Health Research.