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Scientists examining genetics underlying wound healing

Researchers in the Department of Surgery at the Ohio State University Medical Center are using a new technology to examine why some wounds heal quickly, while others become chronic wounds that last for months and even years.

Called laser capture microdissection (LCM), the new technology is used to procure pure cells from specific microscopic regions of tissue sections. Scientists in the Department of Surgery are using LCM to obtain a single cell from wound samples, in order to study the genetics underlying wound healing.

“Traditionally, in wound healing, there has been no way to tell what’s going on in the wound except by visualization and what a biopsy says — whether it’s infected or cancerous,” says Dr. Gayle M. Gordillo, assistant professor of surgery in the Division of Plastic Surgery and principal investigator of the study, known informally as the “Gene Screen.” “We’re advancing the depth and level of this knowledge in our investigation.”

The study is designed to demonstrate which genes predict healing and which genes are expressed in chronic wounds and predict a failure to heal. The two primary goals of the study are to:

  • Improve the diagnostic screening process, so that physicians can determine at an earlier stage which wounds won’t heal.

  • Identify genetic targets for potential new drugs that could stimulate the wound-healing response.

“Now, because we don’t have that information yet, there’s lots of trial and error in the treatment of chronic wounds,” says Gordillo, director of the plastic surgery research laboratory at Ohio State’s Medical Center and director of research for its Comprehensive Wound Center.

About 1,000 wound tissue samples will be collected for the study at seven U.S. centers affiliated with National Healing Corp., a private Florida company that manages 20 percent of the nation’s wound-healing centers. Ohio State’s Comprehensive Wound Center has a partnership with the corporation.

“This is the first time screening has been done like this in a wound clinic,” says Dr. Chandan K. Sen, professor of surgery, vice chairman for surgical research, and executive director of the Comprehensive Wound Center.

The researchers are taking biopsies from clinic patients with both healing and non-healing wounds and using LCM to study a homogeneous cell population and run a full genome screen.

“The goal is to find out, after already knowing the clinical outcome data, if there’s a relationship between gene expression patterns and healing outcomes,” Sen says.

The laser capture technology allows the scientists to zero in on microvessels, which are expected to develop when tissue is healing. If the microvessels in chronic wound samples don’t develop, the researchers can then examine endothelial cells, which line the vessel walls, to see if there is a genetic basis in the cells for why wounds do or don’t heal.

The results of the research could help reduce the cost of wound care, which is more than $8 billion annually, and improve the quality of life and productivity of patients suffering from chronic wounds.

Ohio State is leading the study in part because the Medical Center houses the infrastructure needed to complete all phases of the study, Gordillo says.

For example, a third team leader, Dr. Sashwati Roy, assistant professor of surgery in the Division of General and Gastrointestinal Surgery, is a molecular biologist with expertise in interpreting the data collected from the genes and identifying candidate genes involved in healing.

“One little genetic mutation can affect a person’s response to medications. The laser capture microdissection is really precise and gives us all the material we need from a single cell,” Roy says.

She also notes that the genetic approach to treatment is particularly important for wounds. Though wounds are not routinely studied as a disease process, they are similar to cancer, she says. “No one wound can be compared to another. In the future we’ll look at the gene expression profile and treat accordingly.”

Originally printed in Surgery Today Newsletter, February 2007.

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