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No longer science fiction, gene therapy for wound healing is the focus of ongoing research

Article-No longer science fiction, gene therapy for wound healing is the focus of ongoing research

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  • Gene therapy for wound healing offers promising benefits to the world of cosmetic surgery

Don't blink, or science might leave you behind. That may seem especially so where genetic engineering is concerned.

Its aspect most germane to cosmetic surgery is gene therapy to optimize wound healing.

GOING VIRAL Interestingly, the natural infection pattern of viruses has made them one vehicle for exploring gene modification. "Basically, you transfect viruses to express certain growth factors and inject them into the wounds," explains June K. Wu, M.D., assistant professor of surgery, Columbia University College of Physicians & Surgeons, New York. From there, "The viruses 'infect' the cells in the tissue [of the mice], and their own cells start expressing these growth factors," which scientists had transfected into the viruses, she explains. Researchers believe that these growth factors are normally low in diabetics, which may in part be responsible for their notoriously slow healing. "So, the increased expression of growth factors — as a result of this viral infection — sort of 'revs up' the healing," Dr. Wu explains.

Thomas A. Mustoe, M.D., F.A.C.S., professor and chief of the Division of Plastic Surgery at Northwestern University, agrees that gene therapy using viruses has promise — but also comes with disadvantages. "In gene therapy, delivery is the key issue, and an area of active research," Dr. Mustoe says. "Viral [adenovirus] gene therapy has had an unfortunate track record when delivered intravenously, but is still the gold standard for high-titer gene delivery; when given locally into a wound, systemic side effects are much less of an issue."

Marc G. Jeschke, M.D., Ph.D., Shriners Burns Hospital for Children, The University of Texas Medical Branch, Department of Surgery, Department of Biochemistry and Molecular Biology, has been intimately involved in some of this wound-healing research, with a specific focus on cholesterol-containing liposome research.

He explains that while virus use in genetic engineering nets successes, he has concerns where wound healing is concerned. "Burn patients and diabetics are already immunocompromised, and it's detrimental to 'overload them' with a viral construct," he tells Cosmetic Surgery Times.

LIPOSOME LESSONS As a result, Dr. Jeschke and colleagues sought an alternative and found liposomes. "Cationic cholesterol-containing liposome is a liposome that contains some cholesterol — this is very attractive because it's nonviral," he explains.

"First we found that in fibroblasts in vitro, it's possible to transfect these cells. Then we found this was also true in vivo in rodent studies."

One of the most intriguing findings in the rat model was that, "these liposomes transfect cells even 10 to 15 cm away from the original injection site. This means that the gene was delivered to and taken up by the cell, and then reproduced."

Moreover, Dr. Jeschke found in examining markers for cell damage and stress, "The liposome-containing cholesterol is actually beneficial [to the cells]. There's some protective effect; the cells look better and have more generation and less inflammation, so we know that it's very important that [a compound] contains cholesterol."

The cholesterol has a small positive electrical charge to it, he explains, and this positive charge moves to negative electrodes — binding to the cell and releasing its charge. "This is why you get this transaction and expression of the gene. We asked, is it taken up by the cell? Yes. Is it then produced by the cell? Yes. It travels to the nucleus, it's transcribed to MRNA and is then translated into protein."

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