Increasing the Odds
Mayo Clinic performs more transplants than any other organization in the country. That experience allows Mayo Clinic scientist-physicians to study stem cells and personalize drugs to fight organ rejection and increase the number of viable lungs.
Immune-Building Stem Cell Research
In the 1970s, when Cesar A. Keller, M.D., started his career in pulmonology, lung transplantation was widely considered science fiction. Now, lung transplantation is a lifesaving option for thousands of people every year, but it’s not perfect, Dr. Keller says. For adults, the five-year survival rate is about 55 percent, according to 2008–2015 lung transplant data from the Department of Health and Human Services.
With the help of philanthropic support, Dr. Keller and colleagues in the Mayo Clinic Center for Regenerative Medicine are trying to solve the most lethal imperfection of lung transplantation, a syndrome called chronic organ rejection.
Moving From Rejection to Acceptance
Chronic rejection is considerably more common in lung transplantation than in other solid organ transplants. This is most likely due to environmental factors, which “the lungs are exposed to continuously, with every breath a patient takes,” Dr. Keller explains.
To solve that challenge, Dr. Keller and his colleagues are using tools that are today’s version of science fiction becoming science fact: stem cells and regenerative medicine.
Stem cells have the ability to repair damaged cells, transform into almost any cell the body needs and temper the immune system. So, Dr. Keller’s team launched an initial clinical study to evaluate safety and dose considerations of stem cell use in lung transplant patients who have chronic organ rejection. Researchers also gathered data on whether the treatment may have potential for improving lung function or slowing the progressive decline in function that occurs with chronic organ rejection.
The study used bone marrow-derived stem cells, which were infused through an IV and circulated to the lungs. The lungs “trap all of the stem cells,” Dr. Keller says. His team is preparing for a larger clinical study that will be based on the initial study results. “It took us seven years from our concept to delivering stem cells to the first patient,” he says. “It’s going to take at least another seven or eight years to see if this is successful.”
Developing Lung Restoration Capabilities
A rendering of the lung restoration center on the Mayo Clinic campus in Jacksonville, Florida.
This research and other activities in the Center for Regenerative Medicine will be extended by another new technology that is coming to the Florida campus. In 2016, Mayo Clinic and United Therapeutics broke ground on a lung restoration center that could more than double the number of donor lungs viable for transplantation in the United States. (Read news release).
United Therapeutics is working to improve donor lungs and make them suitable for transplantation using “ex vivo lung perfusion technology.” The technology stores lungs in a specialized chamber and treats them with solutions and gases that can reverse lung injury and remove excess fluids.
Dr. Keller says the technology, which preserves lungs when they are outside the body, can be used to research the benefits of delivering stem cells to lungs before they are transplanted into a person. That strategy may help reduce immune system responses after the lungs are transplanted. “It was literally all science fiction when I began,” Dr. Keller says. “It’s interesting to think about where the field was when I started and to see these concepts become things we can apply.”
Despite the use of immuno-suppressants, a person’s body at times can recognize the transplanted organ as a foreign object and attempt to protect itself by attacking the new organ. Even with immunosuppression medications, some transplant patients experience episodes of rejection.
There are two main types of rejection:
Chronic rejection occurs over
many years because a patient’s immune system never fully accepts
the transplanted organ and slowly damages it.
Acute rejection may occur from the first week after the transplant to three months afterward.
An Individualized Strategy for Stopping Organ Rejection
The effectiveness of immunosuppressant drugs is governed by a number of factors, but a major contributor is an individual’s genome. The genes that make up each person’s genome direct how a drug is metabolized and how it stimulates the immune system to accept the transplant.
While these drugs help a transplanted organ continue to function, they tax the rest of the body. For transplant patients, it is essential to understand the appropriate regimen of anti-rejection medications.
Mayo Clinic’s Center for Individualized Medicine is collaborating with a molecular diagnostics company to monitor patients after an organ transplant and improve the efficacy of these drugs by tailoring the treatment to an individual’s genome through the TOGETHER trial.
The initial focus is on immunosuppressant therapies for 250 kidney transplant recipients.
“Genomic analysis of blood can reveal early signs of rejection in transplanted kidneys,” says principal researcher Mark D. Stegall, M.D., the James C. Masson Professor of Surgery. “The potential clinical utility is to be able to monitor for rejection more frequently than is possible with surveillance biopsies and to individualize immunosuppression in transplant recipients.”
Among this study cohort, kidney transplant patients will have genomic testing at five intervals throughout their first postoperative year. These data points may help transplant care teams fine-tune immunosuppression drug regimens and improve patient outcomes.
“The promise of individualized medicine is that we can now use information found in a patient’s own genetic code to provide better, more personalized answers about their medical care. Through important efforts such as the TOGETHER trial, we can and will make that promise more of a reality for our transplant patients,” says Alexander S. Parker, Ph.D., the Cecilia and Dan Carmichael Family Associate Director for the Center for Individualized Medicine at Mayo Clinic in Jacksonville, Florida.
This article was originally published in Mayo Clinic Magazine, Volume 1, 2017.