Genetically Altered Skin Cells May Reduce Lethal Infections in Severe Burn Victims
Published February 2007
Burn researchers have created genetically modified skin cells that, when added to cultured skin substitutes, may help fight off potentially lethal infections in patients with severe burns.
Dorothy Supp, PhD, and her team have found that skin cells genetically altered to produce higher levels of a protein known as human beta defensin 4 (HBD4) killed more bacteria than normal skin cells. HBD4 is one in a class of proteins that exist throughout the body as part of its natural defense system.
"Adding these genetically modified cells to bioengineered skin substitutes could provide an important defense system boost during the initial grafting period, when the skin is most susceptible to infection," explains Supp, an adjunct research associate professor at UC and researcher at Cincinnati Shriners Hospital for Children.
Supp believes defensins could become an effective alternative method for burn wound care and infection control. Using them in cultured skin substitutes, she adds, could also decrease a patient's risk for infection, improve skin graft survival and reduce dependence on topical antibiotics.
Researchers reported these findings in the January 2007 issue of Journal of Burn Care and Research.
Cultured skin substitutes are grown in a laboratory using cells from a burn patient's own skin. These cells are cultured, expanded and combined with a spongy layer of collagen to make skin grafts that are reattached to the burn wound.
"Cultured skin substitutes are improving the lives of many burn patients, but they also have limitations-including an increased susceptibility to infection," says Supp. "Because cultured skin grafts aren't connected to the circulatory system at the time of grafting, they aren't immediately exposed to circulating antibiotic drugs or antibodies from the body's immune system to fight off infection."
Currently, physicians manage cultured skin graft infections during the early healing period by continually wrapping the wound in dressings soaked in antimicrobial drugs. Although this protects the grafts, Supp says, it can also contribute to the emergence of drug-resistant strains of bacteria, so better infection control methods are needed to counter this effect.
In a three-year laboratory study, Supp isolated the HBD4 gene from donated tissue samples and transferred it into surface skin cells to give them enhanced infection-fighting abilities. These cells were then infected with Pseudomonas aeruginosa, a type of bacterium found commonly in hospitals, and allowed to incubate. Analysis revealed that the genetically altered cells containing HBD4 were more resistant to microbial infections than the unaltered cells.
"If it proves effective in additional testing," Supp predicts, "this type of gene therapy could be a promising alternative infection-control method for burn wounds."
Researchers hope to begin testing this approach in an animal model this year.
The study was funded by Shriners Hospitals for Children. Coauthors include Jason Gardner, Jennifer Klingenberg and Andrea Smiley, of Shriners, and Alice Neely, PhD, of Shriners and UC.