New project explores whether skin wounds can heal without leaving scars

Can skin wounds heal without leaving scars? That's the question being explored in a project entitled ScarLessWorld headed by Dr. Yuval Rinkevich, research group leader at Helmholtz Zentrum München. His work will now be supported by a Consolidator grant from the European Research Council (ERC) providing around two million euros of research funding over the next five years.

People have been fascinated by tissue and organ regeneration for thousands of years. "So it's all the more surprising that this process is still relatively poorly understood," notes Yuval Rinkevich. He heads the Cellular Therapeutics in Chronic Lung Disease research group at the Institute of Lung Biology and Disease at Helmholtz Zentrum München.

He and his team have recently made a major contribution to this field. "We were able to show that fibroblasts - the connective tissue cells of the skin which are responsible for wound healing - are not a uniform population," explains Rinkevich. "Our findings show that there are four different types and that it is the composition of these four types which determines how much scarring occurs."

Rinkevich gives an example, "If the skin of a developing embryo gets injured, it simply regenerates. In later life stages, however, the wound scars." The researchers recently succeeded in demonstrating that this phenomenon is due to differences in the population of fibroblasts in the skin. The proportion of regenerative cells decreases as development progresses, whilst the number of scar-forming cells increases. When the researchers transplanted fibroblasts from mouse embryos into wounds in adult animals, scarring was significantly reduced.

Building on these results, Yuval Rinkevich knows what he wants to achieve next, "We want to use new experimental approaches to understand how this scarless wound healing works and, in the long-term, to reproduce it clinically." As part of his ScarLessWorld project, he and his team are now planning

• to fully catalogue the repertoires of dermal fibroblast lineages,
• to use imaging techniques to determine fibroblast dynamics during wound healing,
• to identify the genes responsible for regeneration vs. scarring,
• and finally, to translate these findings to human skin.

"Using the technologies we have developed, we can achieve this breakthrough. That would be a huge leap forward for regenerative medicine," says Rinkevich. Options for preventing scar formation in large wounds, burns and similar injuries are currently extremely limited. If the approach proves to be successful, it could possibly also be adapted to other conditions, such as lung fibrosis, in which the lung tissue is scarred.