'Gene Screen' Hopes to Find the 'Why' Behind Wound HealingCOLUMBUS, Ohio – Emerging technology is assisting Ohio State University Medical Center researchers in their quest to find out why some wounds heal quickly and others become chronic sores that can last for months or even years. A team of scientists is using laser capture microdissection to pluck a single cell from wound samples to boil the search down to the genetics behind wound-healing activity. “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. We’re advancing the depth and level of this knowledge in our investigation,” said Dr. Gayle Gordillo, director of the plastic surgery research lab at Ohio State’s Medical Center and principal investigator of the study, informally called the “Gene Screen.” This analysis is designed to demonstrate which genes predict healing and which genes are expressed in wounds that are chronic and predict a failure to heal. The study leaders have two primary goals: to improve the diagnostic screening process so physicians can determine earlier which wounds won’t heal, and to 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,” Gordillo said. The results of the research could help reduce the cost of wound care, which tops an estimated $8 billion annually, and help improve the quality of life and work productivity for the roughly 2 percent of Americans at any given time who are suffering with a difficult wound. Approximately 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 National Healing Corp. “This is the first time screening is being done like this in a wound clinic,” said Dr. Chandan Sen, executive director of Ohio State’s Comprehensive Wound Center and professor and vice chair of surgery. The researchers are taking biopsies from clinic patients with both healing and non-healing wounds and using the laser capture microdissection 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 – to see if there’s a relationship between gene expression patterns and healing outcomes,” said Sen, also deputy director of Ohio State’s Davis Heart and Lung Research Institute. The laser capture technology allows the scientists to zero in on the microvessels, which are expected to sprout when tissue is healing. If the microvessels in chronic wound samples are not sprouting, the researchers can then turn to endothelial cells – which line the vessel walls – to see if there is a genetic basis in those cells for why wounds do or don’t heal. Ohio State is leading the study in part because its medical center houses the infrastructure needed to complete all phases of the study, said Gordillo, director of research for the Comprehensive Wound Center. For example, a third team leader, Dr. Sashwati Roy, assistant professor of surgery, is a molecular biologist whose expertise lies in sorting out the meaning of 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. But the main problem of studying gene expression is that it generates oceans of data,” Roy said. She also noted that the genetic approach to treatment is particularly important for wounds, which, though not routinely studied as a disease process, are similar to cancer. “No one wound can be compared to another. In the future we’ll look at the gene expression profile and treat accordingly,” she said. Dr. Sorabh Khandelwal, an emergency medicine physician and director of hyperbaric medicine at Ohio State’s Medical Center, looks forward to applying the results of the research. “Wound care until recently has been treated under a one-treatment-fits-all mentality. Wound care as a specialty is still new,” Khandelwal said. Current treatment methods include “looking at the patient as a whole, as an individual, and forgetting about the wound at first,” he said. Physicians urge patients to stop smoking and help them improve nutritionally so their protein stores are at appropriate levels. They examine the wound to ensure it’s not cancer or another skin condition masquerading as an ulcer, and check to see that blood flow is getting to the wound. They then attack the wound with specialized dressings, antimicrobials, enzymatic drugs that break down dead tissue, or growth factors, all agents that help the body heal itself. A subset of patients receives hyperbaric oxygen therapy. Ohio State’s Medical Center houses the first clinical program in the country to receive Level 1 certification from the U.S. Food and Drug Administration in the use of negative pressure therapy for wounds. The quality of care is high, but Khandelwal said he hopes the Gene Screen will add yet another layer of sophistication to the clinical approach to wound care. “Genetics will help because one of the things we can’t answer is, ‘Why do some patients heal and some don’t?’ We as experts can guess, but we don’t know the real reason.”
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