Wednesday January 23 2008
The gel reduced scarring in mice
“A gel that can help wounds heal faster and reduce scarring is being developed by British scientists,” the Daily Mail reported today. Channel 4 and BBC News said that the gel accelerates wound healing by increasing the regeneration of blood vessels around the wound and speeding up tissue reconstruction. They say that it works by suppressing a gene known as osteopontin (OPN), which also triggers scarring. It is believed that the new development could help those who would otherwise have been scarred by their wounds, and also those who suffer internal damage to organ tissue through illness or surgery.
These are very early developments in the use of a gel to suppress OPN and promote improved wound healing and reduced scarring. Although these are promising findings, this research is in mice only. As there are differences between the species in how wounds heal, further research is needed before the practical application to humans is made clear.
Where did the story come from?
Ryoichi Mori and colleagues from the departments of Physiology and Biochemistry, School of Medical Sciences, at the University of Bristol carried out the research. The study was funded by the Wellcome Trust, Uehara Memorial Foundation, Nakotomi Foundation and Japan Society for the Promotion of Science Post-doctoral Fellowships for Research Abroad, and a Marie Curie Fellowship.
The study was published in the peer-reviewed: Journal of Experimental Medicine.
What kind of scientific study was this?
This was an experimental study conducted in laboratory mice. From previous studies, researchers expected that a protein called osteopontin (OPN) played a role in scarring and that this protein is only produced when there is an inflammatory response to a wound. Because of this connection with inflammation, the researchers were also interested in seeing whether white blood cells, and which white blood cells, were responsible for turning on the expression of OPN. They therefore hoped to find potential targets for treatments that would switch off the expression of OPN and ultimately improve the speed and quality of wound healing.
The researchers examined a group of mice who had been humanely inflicted with wounds to their backs. They were interested in what effects a Pluronic gel – a gel which contains an enzyme (AS ODN) that can block the expression of OPN – would have on wound healing, inflammation and the concentration of white blood cells. They compared levels of OPN production and the presence of white blood cells in the wounds (through use of a fluorescent marker and by examining the wound tissue from biopsies under a microscope) between mice whose wounds had been treated with the gel and others that had received a placebo treatment. They also compared the rate and quality of wound healing between the groups and the levels of collagen and other granular tissues that are involved in scarring.
In other parts of the experiment, the researchers explored in more depth which white blood cells were responsible for switching on the production of OPN.
What were the results of the study?
The researchers found that, compared to normal wound healing, treatment with the gel led to a 25 per cent decrease in concentration of OPN in the wound tissue six hours after injury, and a 50 per cent reduction three days later. Microscopic analysis of the wounded tissue showed that the treated wounds had faster skin regeneration. Greater contraction of connective tissue and a reduced area of granulation in the middle of the wound indicated improved closure of the wound and reduced scarring.
After three weeks, the researchers found that mice treated with the gel had reduced scarring in their treated wounds compared to untreated controls. At times when they would normally expect the number of white blood cells (neutrophils and macrophages) to be at peak levels following injury, they found the number was reduced in the treated tissue compared to the controls. There also appeared to be evidence of increased new blood vessel growth in the treated tissue.
The researchers said these findings suggest it is likely that a type of white blood cell called macrophage are responsible for turning on production of OPN. This is through a particular substance (platelet-derived growth factor [PDGF]) that these cells release. The researchers confirmed the involvement of PDGF by using an antibody (Gleevec) to neutralise PDGF and finding that OPN production was subsequently reduced.
What interpretations did the researchers draw from these results?
The authors conclude from their research that optimum wound repair may be hindered by inflammatory cells triggering the production of OPN in the wound which increases scar development. They suggest that “OPN and PDGF are potential targets for therapeutic modulation of skin repair to improve healing rate and quality”.
What does the NHS Knowledge Service make of this study?
This research used recognised methods to explore - at a molecular level –the mechanisms of wound healing. The findings from this study will be of particular interest to the scientific community as they shed light on the complex processes underlying wound healing.
In some parts of the experiment, judgements made on the extent of scar tissue, wound area and appearance, are largely subjective. As the authors themselves acknowledge, they are not making any claims that the mechanisms that they have identified are the only ones involved in the wound healing process and in the formation of scar tissue.
In terms of their application to human healing, these findings will hopefully lead to studies in man. However, until studies in humans take place, it is not clear how soon a gel treatment to improve wound healing will be available. Differences in the mechanisms of wound healing between the species could affect the applicability of the findings.
Sir Muir Gray adds...
Bring on the human beings.