Cheese-making bacteria have been engineered to produce skin repair proteins that promote rapid healing when applied to wounds in mice. A clinical trial is now under way to see if they can help to heal chronic wounds that can develop in people with diabetes.
About a quarter of people with diabetes end up with open wounds called ulcers that don’t heal because of poor circulation and other complications. In severe cases, the affected body part – usually a foot – must be amputated.
at Aurealis Therapeutics, a company in Finland, and his colleagues wondered if wound healing could be improved by administering proteins that are involved in skin repair.
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Instead of injecting these into wounds, their idea was to genetically engineer bacteria that could continuously produce the proteins once applied to damaged tissue.
They used Lactococcus lactis bacteria, which are used in cheesemaking and considered highly unlikely to trigger unwanted health effects in people. The researchers genetically engineered the bacteria so they would produce three skin-healing proteins: fibroblast growth factor-2, interleukin-4 and colony stimulating factor-1.
As a test, the team applied these bacteria to 1-centimetre-wide wounds on mice that mimicked diabetic ulcers. After a week of daily applications, the wounds were almost fully closed. In contrast, wounds treated with an inactive substance barely closed at all.
Analysis under a microscope showed that the engineered bacteria accelerated wound healing by recruiting immune cells, promoting blood vessel growth and boosting the activity of cells called fibroblasts that form connective tissue.
No major side-effects were observed in the mice.
Kurkipuro and his colleagues are now testing the genetically engineered bacteria in people with diabetic foot ulcers as part of a clinical trial in Germany and Poland.
Currently, most diabetic foot ulcers are treated by cutting away dead skin, applying dressings and giving antibiotics. Newer treatments include hyperbaric oxygen therapy, negative wound pressure therapy, electrical stimulation, growth factors and bioengineered skin, but these are often expensive or have limited efficacy.
PLoS One
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