Wound Healing: A Flawless Future

7. February 2017
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Wounds leave scars behind. However that situation could soon change. Cell biologists have discovered a natural healing process that can regrow injured skin, leaving it scar-free. The key to this lies in the regeneration of hair follicles and fat cells.

One falls from a climbing rig, gets a new hip joint, ends up in a motorcycle accident – these and such other life events leave scars in their track. And these scars can be unsightly, itchy and sometimes even painful. Their presence provides a constant reminder to their carriers as well as their observers of the often unfortunate situations in which they originated. However those bead forming, discolouring and hair killing events in our past could soon become a part of history themselves, as scientists report in the current issue of Science.

Animal studies: Large wounds heal without scarring

Researchers at the University of California, Irvine, and the University of Pennsylvania have in their studies of mice identified cellular and molecular processes in which large wounds in adult mice developed into almost normal looking skin with new hair follicles and adipose tissue. Ultimately, the centre of the wound was hardly distinguishable from normal, unscathed skin. How was this possible?

Christian F. Guerrero Juarez from the University of Pennsylvania explains: “Typically one mainly find myofibroblasts in wounds. It had been assumed until now that myofibroblasts cannot transform into other cell types, and can therefore solely form scar tissue. We were able to show that they are not quite like that”.

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Christian F. Guerrero-Juarez (links) and Maksim Plikus, © Raul Ramos / UCI

Previously unthinkable: converting myofibroblasts into adipocytes

The scientists first succeeded in the step of converting myofibroblasts into fat cells in their laboratory. Fat cells do not form any scar tissue. They occur naturally in the skin, but not when wounds heal into scars.

Scar tissue also differs in another aspect from healthy skin: in scar tissue there are no hair follicles. This fundamental difference was the basis for further action by the scientists.

Hair follicles to begin with

“We can now manipulate wound healing so that instead of scarring taking place a regeneration of the skin occurs”, says study leader George Cotsarelis from the University of Pennsylvania. The secret lies in regenerating the follicles to begin with, he says. “Following that, in response to signals from the follicles the fat also regenerates”, says Cotsarelis, explaining the process.

The study showed that hair and fat do indeed develop separately, but not independently from one another. First, the hair follicles form. The regenerating hair follicles stimulate the surrounding myofibroblasts to regenerate as fat, instead of forming scar tissue. “Without hair follicles the conversion of myofibroblasts into adipocytes does not take place. The new fat cells are indistinguishable from already existing fat cells. That makes the healing wound naturally not look like a scar”, the researchers write.

Video on the study:

BMP provides signal for conversion

The researchers have identified a bone morphogenetic protein (BMP) to be an essential factor in the communication between hair follicles and fat cells. The protein belongs to a group of growth factors, the cytokines, and instructs the myofibroblasts to convert into fat cells.

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Adipocytes arise in wound tissue only when hair follicles emit a particular signal © George Cotsarelis

Transformation also works in humans

“Our findings from experiments with mice can be transferred to humans”, said Maksim Plikus from the University of California, adding: “In the cell culture bringing human fibroblasts from keloids, a particular cell type, into contact with either pure BMP or human hair follicles is sufficient in order to trigger their transformation to adipocytes”.

A loss of adipocytes in the skin is common, and has thus far not been able to be treated satisfactorily. On the one hand, adipocyte loss can result from therapy, for example against HIV, but is also a natural process over the course of life. Hence it is believed that deep wrinkles originate through the steady loss of skin lipids. Without its underpinning fat layer, the skin shrinks and folds like a balloon losing air. These new findings could also benefit, in addition to scar-afflicted people and those with lipo-dystrophies, the anti-ageing fan.

Fat cells have long had a purely negative image. This is firstly due to the fact that being fat is frowned upon, and secondly due to the numerous health risks that are associated with having too much body fat. Yet the human body is dependent on fat not only as an energy store, but also uses the adipose tissue as an endocrine organ, which pours out numerous highly active substances.

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Formation of scar-free tissue with hair over time © George Cotsarelis

Injections or creams

In a subsequent step, the findings need to make their way from the laboratory to application. “This could theoretically simply occur via an injection which passes the signal molecules directly into the scar, for example by using a small insulin syringe as currently also used for Botox applications”, says Plikus. Creams are also conceivable, into which low molecular weight agonists and antagonists which control the metabolic steps of fat cell formation control have been processed.

 

Source:

Regeneration of fat cells from myofibroblasts during wound healing.

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