Gene Therapy Tackles Severe Burns

Jan. 29, 2007 — Severe burns are not only painful, they also put patients at risk of serious infection. Now researchers are using gene therapy to rev up the wound healing process in skin cells, hoping to fight potentially lethal infections.

"The gene we're using is found in humans, but not normally turned on in the skin," explained Dorothy Supp, a researcher at Cincinnati Shriner's Hospital for Children and the University of Cincinnati. "We transferred it to skin cells in culture increase their antimicrobial function."

Supp and her team published the research in the current issue of the Journal of Burn Care and Research.

The technique could prove especially therapeutic for patients with burns covering more than half of their bodies.

In these cases, doctors often use skin cells from the patient to grow more cells in a laboratory. The new cells are then combined with a sponge-like substance to make a cultured skin substitute.

The doctor uses the skin substitute as a graft, which the body recognizes as its own. The good news is that the body won't produce an immune response. The bad news is that because the cultured skin doesn't have blood vessels, it can't respond to oral antibiotics given to the patient to manage infections.

To get around the problem, doctors usually wrap the wound in dressings soaked in antimicrobial drugs. But the practice is not a guarantee against infection and it can contribute to the emergence of drug-resistant bacteria.

Instead of fighting infection from the outside, Supp and her team wanted to find a method that worked from the inside — gene therapy.

They had read about a gene called HBD4, normally found in other parts of the body, such as the male reproductive tract.

The gene is activated naturally when an area becomes inflamed or in the presence of microorganisms. When the gene turns on, it produces a protein that essentially pokes holes in the cell membrane of the bacteria, killing it.

Supp and her team isolated HBD4 and transferred it to skin cells. Next, they allowed the cells to divide and multiply into a larger colony — each new cell containing HBD4.

Lastly, they exposed the genetically engineered cells to bacteria strains common in hospitals.

The researchers saw a 25 percent reduction in bacteria in the modified cells, when compared to skin cells that had not been modified. Supp thinks that even if the engineered skin cells don't kill every microorganism, they may weaken the bacteria enough to make it more susceptible to antibiotics.

But infection is not the only problem facing skin grafts in burn patients, said Ludwik Branski, a burns research fellow at Shriners Hospital for Children in Galveston, Texas. Skin grafts themselves are extremely fragile, he pointed out.

"From a clinical perspective, the improvement of cultured skin substitutes in terms of an innate resistance against bacterial infection might help the patient," said Branski, "but most probably will not solve the more technical problems of graft breakdown and graft loss."

Eventually, Supp would like to combine the engineered cells with the sponge-like collagen to make a cultured skin substitute. She hopes to begin testing this approach in lab animals by early 2007.