Goal is to Help Patients Tolerate Transplants Without Anti-Rejection Drugs
Researchers at the University of Maryland School of Medicine and the Naval Medical Research Center have begun a novel research collaboration to develop and test new ways to prevent rejection of a transplanted organ or tissue without suppressing the person’s immune system. The goal of the project, to be funded by $24 million in grants from the Office of Naval Research for the next five years, is to adapt transplant therapies, commonly used to replace diseased organs, to injuries that often result from combat.
If successful, this project will make it easier for physicians to replace limbs or other large areas of tissue, such as skin from burns or chemical injuries, with transplanted tissue. Such repairs could give combat injured veterans a better chance at a full functional recovery and be more cosmetically appealing. Currently, these types of injuries usually are treated with prosthetic devices or partial skin grafts.
“We plan to find effective methods to transplant healthy tissue to replace tissues lost as a result of service-related injuries,” says Stephen T. Bartlett, M.D., professor of surgery and medicine and head of the Division of Transplantation at the University of Maryland School of Medicine. Dr. Bartlett is one of the lead investigators in this project.
“Results of our work will benefit all patients who need organ or tissue transplants,” adds Dr. Bartlett, who is the chief of Transplant Surgery at the University of Maryland Medical Center in Baltimore, which has the largest kidney transplant program in the United States.
Currently, people who receive an organ or tissue transplant must take powerful anti-rejection drugs that suppress the immune system and make them more at risk of infections, cancer, and other health complications. Higher doses of these powerful drugs are necessary for people who need donor tissue transplants following traumatic injuries or after extensive, disfiguring surgery that may be required in order to save someone’s life. Such tissues include skin, muscle, bone and blood vessels and are referred to as composite tissue transplants.
“About 10 to 15 percent of all combat-related injuries lead to a major loss of tissue that could potentially benefit from composite tissue transplantation,” says Allan D. Kirk, M.D., Ph.D., from the Navy Medical Research Center Transplantation Laboratory and one of the lead investigators in the project.
“Unfortunately, the medications required to prevent rejection of these types of transplants are too toxic to justify their use in non-life threatening conditions. In addition, composite tissue grafts seem to be more vigorously rejected and tend to need better anti-rejection therapy than is available today. By improving our ability to prevent rejection without the use of immune suppressing drugs, transplant therapies could be applied to more conditions,” says Dr. Kirk.
“We will be testing many approaches in the laboratory and in clinical trials. In general, we will be targeting specific cells or receptors rather than the entire immune system. This targeted approach would enable the rest of the immune system to function more normally,” according to Dr. Bartlett.
A key feature of the research will be to test the elimination of corticosteroid drugs following a transplant. These drugs can cause serious side effects, including diabetes, hypertension, bone thinning, weight gain and cataracts. If their use can be stopped safely, it would be especially beneficial for patients who need composite tissue transplants because corticosteroids impair wound healing.
“We are delighted to have the University of Maryland as our partner in this research,” says Dr. Kirk. “The R Adams Cowley Shock Trauma Center and the Joseph and Corinne Schwartz Division of Transplantation at the University of Maryland Medical Center are recognized centers of excellence in both trauma and transplantation care. The Naval Medical Research Center has a highly sophisticated research program to study the effect of new agents on preventing rejection without traditional drugs that suppress the immune system. Combining the resources of both centers makes good sense to improve the potential therapies for injured service men and women.”
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