Therapy keeps lungs healthy, even after death
October 29, 2009
Noor Javed
STAFF REPORTER
A pair of lungs sits outside the human body in a bubble-like apparatus, seemingly breathing on their own.
The lungs move in and out as an oxygen- and protein-rich fluid is pumped into the organ to keep it from deteriorating. This process does the job for up to 12 hours. After that, the race is on to get the donor organ into a recipient because the tissue will start to deteriorate, the lung cavity will get flooded and the tissue walls will begin to separate – making it unusable for transplantation.
But now, after 10 years of research, a team of Toronto scientists has discovered a way to genetically modify the injured donor lungs, so that they repair on their own any damage that happens once death occurs and before a transplant takes place.
The revolutionary gene therapy technique was described in the latest edition of the journal Science Translational Medicine, which was published Wednesday.
The technique could double the number and improve the quality of donor lungs – and other donor organs – available for transplant and dramatically improve health outcomes after transplantation
"We are actually able to have the organ improve over time while it is outside the body," said Dr. Shaf Keshavjee, senior scientist at the McEwen Centre for Regenerative Medicine and director of the University Health Network's Lung Transplant Program.
Last year, Keshavjee and his team pioneered a technique dubbed the Toronto XVIVO Perfusion System, which preserved lungs in a structure, pumped them with an oxygen- and protein-rich solution and attached them to a respirator – essentially mimicking the physiology of real lungs. The procedure increased the "shelf life" of the lungs to nearly 12 hours from four, and set the stage for the use of a sophisticated gene therapy technique.
Researchers, all from hospitals in Toronto, found that lungs maintained on the perfusion system alone were stable for up to 12 hours. But the lungs that received the gene therapy, in addition to the perfusion, significantly improved their functions, including the flow of oxygen and blood in the lungs. "For the first time, we hope to improve the health of donor lungs that we could not have used before by using gene therapy to decrease inflammation and repair cells before transplantation," said Keshavjee.
Worldwide, only 15 per cent of donor lungs are usable due to injuries sustained by the organ during the death of the donor.
The researchers used pig and human donor lungs by first placing them in the perfusion system to warm them to normal body temperature.
The lungs were then injected with the IL-10 gene, which prevents organ degeneration and shuts off cells that cause the body to refuse transplanted organs.
They discovered that the lungs began to produce the new IL-10 anti-inflammatory proteins six hours after insertion, and began to decrease inflammation in the lungs, repair the structure and prepare the organ for potential rejection it will face post-transplantation.
Scientists say that donor lungs that function better from the start will lead to more predictable and safer outcomes, shorter periods of mechanical ventilation and shorter periods of post-operative care.
Toronto has been at the forefront of lung transplantations for decades. In 1983, Toronto researchers were the first in the world to complete a successful lung transplant. A few years later, they did the world's first double-lung transplant.
But their latest research has implications beyond lungs.
"This is really the next level of modifying the organs to work better or creating genetically engineered organs," said Keshavjee.
The therapy can eventually be applied to other organs, like the kidney, liver and heart, he said.
Currently, more than 50 people are waiting for either a lung or heart transplant in Ontario. About 20 per cent of them will die on the waiting list.
Toronto Star