Research Profile – Avoiding Rejection

A new skin substitute could help treat severe burns.

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A prototype skin substitute developed by researchers in Vancouver may be just what the doctor ordered for replacing skin that has been severely damaged. The substitute contains the key components that make up naturally occurring skin but has the added feature that it won't be rejected by a patient's immune system.

It could become an off-the-shelf biological skin substitute useful for any patient who needs it, according to Dr. Aziz Ghahary, a professor in the Department of Surgery and Plastic Surgery at the University of British Columbia. He is also director of the BC Professional Firefighters Burn and Wound Healing Research Group.

Rejection of transplanted skin has been a big obstacle when it comes to treating burn victims. But large burns left uncovered can lead to potentially life-threatening complications, including infections and fluid and heat loss.

The new skin substitute is compatible with the patient's body because it contains an enzyme called IDO. This enzyme, which is found in the placenta during pregnancy, prevents a mother's body from rejecting a developing fetus. It breaks down an essential amino acid, tryptophan, which is needed for survival of immune cells. Depletion of tryptophan within the placenta during pregnancy paralyzes immune cells to protect the fetus.

"So, we cloned the gene for IDO and we put it into skin cells to see if IDO would function in the skin's environment, and whether it would prevent transplanted skin from being rejected," says Dr. Ghahary.

In laboratory studies, supported in part by the Canadian Institutes of Health Research, the UBC researchers found that the skin cells with the cloned IDO gene contained lower levels of tryptophan, which in turn caused nearby immune cells to become inactive.

The team then made a biological skin substitute that mimics what is found on the body naturally. It consists of collagen, keratinocytes and fibroblasts and contains the IDO gene. When the team tested it on wounds in animal models, they found that it was not rejected.

Studies show it may be possible to produce a skin that can be grown in a lab, and applied to any patient who needs replacement skin. "Patients could receive this right away instead of waiting the six weeks it normally takes to grow a compatible skin replacement like it does now," says Dr. Ghahary.

While IDO blocks the action of the immune system from attacking the biological skin substitute, it doesn't interfere with the parts of the immune system needed for wound healing and fighting off infection.

"The particular cells that are involved in rejection are only a small fraction of cells that are important in [immune function]. The majority of immune cells are still intact. The patient's immune system is not going to be compromised with this approach using IDO in the transplanted skin," he notes.

More can be done using the IDO gene and a skin scaffolding, says Dr. Ghahary. The research team is also investigating the possibility of a skin-like scaffolding that contains the IDO gene and insulin-producing cells as a potential treatment for diabetes.

Beyond that, "we're hoping that one day we could use it for solid organ transplants as well," he concludes.

"The patient's immune system is not going to be compromised with this approach using IDO in the transplanted skin... we're hoping that one day we could use it for solid organ transplants as well."
– Dr. Aziz Ghahary, University of British Columbia