Columbia University Wound Healing Center and Researchers at the Weill Cornell College of Medicine Locate Targets in the Fight Against Chronic Wounds

Harold Brem, MD, Director of the Wound Healing Center at Columbia University and Marjana Tomic-Canic, PhD from the Hospital for Special Surgery of the Weill Cornell College of Medicine have made a discovery that could help explain why chronic wounds do not heal. The researchers discovered that skin cells become stuck in the middle of the normal healing process and cannot migrate to the site of the wound in order to close it. The findings, reported in the May, 2006 Journal of Wound Repair and Regeneration and presented at The Wound Healing Society Annual Meeting, could lead to more effective treatments for chronic wounds and potentially pinpoint who will not heal and why.

Neither a patient nor a patient's caregivers are to be blamed for a non-healing wound, says Marjana Tomic-Canic, Ph.D., Associate Professor of Cell and Molecular Biology Dermatology at Cornell University and Associate Scientist at the Hospital for Special Surgery. "If a wound does not heal it is not because a patient is not compliant. Simply put, the biological program fails, and we still don't know why this happens on the molecular level." Frequent among the elderly, people with metabolic problems such as diabetes or obesity, and people who are bed-bound, chronic wounds can lead to infections and limb amputations.

The Columbia and Cornell researchers studied epidermal cells from chronic wound biopsies from patients treated at the Columbia Wound Healing Center. In normal skin, cells are tightly stuck together in order to create a barrier between the body and the outside world, keeping water in and infections out. But when there is a wound, skin cells from lower layers loosen from their neighbors, start migrating to the wound site and begin dividing rapidly. The researchers found that in skin with chronic wounds, the cells multiply even more than is normal, but they are unable to migrate into the wound to close it. Instead, they form thickened layers around the edge, much like a callus or a corn.

Also, in normal skin growth, there are several layers, and cells travel from the bottom out to the surface. As they move upwards, these cells lose their nuclei and form sturdy layers of cross-linked proteins forming a barrier. But in chronic wounds, the researchers found that skin cells are unable to progress to this stage of differentiation, and their nuclei remain present. "The biology seems to be stuck in the middle of these two processes, and can't seem to complete either of them," says Dr. Tomic-Canic.

The Columbia/Cornell research team previously discovered that this stalling-out of the healing process, is caused by a molecule called c-myc. This molecule can both suppress cell migration and cause thickening of skin layers, and the researchers found high levels of it in chronic wound tissue, in layers of skin where it is not normally supposed to be.

Dr. Brem says that the molecules the team has identified can make the treatment of chronic wounds more effective by determining how much tissue should be removed when dressing a wound. By testing skin cells for high levels of molecules such as c-myc, physicians would be able to tell which cells are in the non-healing state and to remove the non-healing tissue, while retaining the healthy portion. "In the future, this discovery will allow us to diagnose the specific mechanism of a wound that is not healing with an outpatient test as simple as a urinalysis or pregnancy test, and treatment will be as trouble-free as treating any simple dermatologic condition. These capabilities may still be a decade away, but this discovery shows there is promise to end the epidemic of chronic wounds," he says.

Such markers may also be useful in clinical trials of new therapies for non healing wounds such as venous ulcers, diabetic foot ulcers and pressure ulcers, to make sure that the treatments are targeting the right types of cells. In the future, molecules such as c-myc and beta-catenin could be the focus of medications for bedsores, to cut the chain of wound development before it becomes advanced.