For the first time, a team of scientists in Canada have successfully used gene therapy to repair injured human donor lungs, making them potentially suitable for transplantation into patients.
This technique could significantly expand the number of donor lungs by using organs that are currently discarded, and improve outcomes after transplantation, according to researchers at Toronto's McEwen Centre for Regenerative Medicine, University Health Network.
The research team, led by Dr. Shaf Keshavjee, developed a technique of ex vivo gene delivery to donor lungs, before they are implanted into a recipient's body. The technique was shown to be simple and effective in improving lung function.
"This work is a big step in using regenerative strategies to repair injured 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," Dr. Keshavjee said.
Using a novel approach to overcome some of the challenges of gene therapy, the researchers first developed a strategy to preserve lungs at normal body temperature, with the lungs kept outside the body in a protective dome.
The Toronto XVIVO Lung Perfusion System continuously pumps a bloodless solution of oxygen, proteins and nutrients into injured donor lungs, mimicking normal physiological conditions.
This makes it possible for the injured cells to begin repairing themselves, and also sets the stage for more sophisticated repair techniques to be applied to donor lungs.
Working with pig and then human donor lungs, which were unsuitable for transplantation, the researchers first placed the lungs on the Toronto XVIVO Lung Perfusion System to warm them to normal body temperature.
Then, using a specially engineered adenovirus vector-a common cold virus-the researchers used a bronchoscope to inject the vector with an added IL-10 gene through the windpipe into the human lungs.
The study found that lungs maintained on the Toronto Lung Perfusion System alone, the control group, did not deteriorate and remained stable.
However, the donor lungs that received the gene therapy, in addition to the ex vivo perfusion, significantly improved their function with regards to blood flow throughout the lungs and their ability to take in fresh oxygen and get rid of carbon dioxide.
The boosted IL-10 effect lasts for up to 30 days in the lung. The authors state that transplanting lungs which function better from the start would lead to more predictable, safer outcomes, shorter periods of mechanical ventilation and shorter intensive care unit stays for patients.
Dr. Keshavjee emphasizes that clinical trials on humans would be the next step in testing this promising approach before it could be used on patients waiting for lung transplants.
"This work opens the door for a variety of therapies that could potentially be applied to repair various injuries in other donor organs to improve the safety and outcome of transplants," Dr. Keshavjee said.
The results are published in the October 28, 2009 edition of the journal Science Translational Medicine.