Genetically Altered Cells May Help Artificial Skin Fight Infection

Title: Genetically Altered Cells May Help Artificial Skin Fight Infection
Author: Amanda Harper
Date of Publication: January 9, 2007
Published in: Journal of Burn Care and Research
Study funded by: Shriners Hospitals for Children

Dorothy Supp, PhD and her burn research team in Cincinnati 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. They found that skin cells genetically altered to make higher levels of the tiny protein human beta defensin 4 (HBD4), which naturally exist in the body as part of its defense system, were able to kill more bacteria than normal skin cells. This is important because infections are a serious risk for patients who have recently received skin grafts.

The cells are taken from the patients’ own skin, cultured in a laboratory, then are expanded and combined with a spongy layer of collagen to make the actual skin grafts that can be reattached to the wound. It is good that the cells are taken from the patients’ own skin because the patients won’t have to deal with seeing someone else’s skin on their body, which while medically effective has proven to be somewhat psychologically damaging. These psychological effects were seen in one of our lectures where hand amputatee and had another man’s hand sewn on to his residual limb. While surgeons spent many painstaking hours attaching each blood vessel and nerve ending from the new hand to this man’s arm and the hand was functioning beautifully, the man could not deal with the psychological trauma of seeing another man’s hand instead of his own, and actually opted to get the hand removed and chose to have a prosthetic attached instead. However, what if the patient is so badly burned that there isn’t enough healthy skin from which to take cells to culture? Should the necessary skin cells come from a cadaver or an animal?

Supp has been conducting her study for three years and has learned how to successfully isolate the HBD4 gene from donated tissue samples and transfer it into surface skin cells, called keratinocytes, to give them enhanced infection-fighting abilities. These cells are then infected with pseudomonas aeruginosa, a type of bacteria most commonly found in hospitals, and allowed to incubate. When analyzed, Supp discovered that the genetically altered cells containing HBD4 were more resistant to microbial infections that the unaltered cells. These cells, if effective, could become an alternative method for burn wound care as well as for infection control in general.

If they are used in cultured skin substitutes, they may also decrease the patients’ risk for infection, improve skin graft survival and hopefully reduce the patients’ need for antibiotic treatment. Currently, physicians have to continually wrap the skin graft surgical wound in dressings coated in antimicrobial drugs to fight off infection. This is a time consuming process that does not necessarily rule out infection since antibiotics have to be given to the patient topically and orally, increasing the risk of the emergence of drug-resistant strains of bacteria.

The goal is to add these genetically modified cells to bioengineered skin substitutes in the hopes that they will provide an essential boost to the body’s natural defense system during the initial grafting period, when the skin is most susceptible to infection. However, cultured skin substitutes do have an increased susceptibility to infection since they are not yet connected to the body’s circulatory system at the time of grafting, and are therefore not able to circulate antibiotic drugs or antibodies from the body’s immune system to fight off infection.