Using fat to help wounds heal without scars

January 5, 2017, Perelman School of Medicine at the University of Pennsylvania
Comparison of wounds healing with and without hair follicles. Credit: Penn Medicine

Doctors have found a way to manipulate wounds to heal as regenerated skin rather than scar tissue. The method involves transforming the most common type of cells found in wounds into fat cells - something that was previously thought to be impossible in humans. Researchers began this work at the Perelman School of Medicine at the University of Pennsylvania, which led to a large-scale, multi-year study in connection with the Plikus Laboratory for Developmental and Regenerative Biology at the University of California, Irvine. They published their findings online in the journal Science on Thursday, January 5th, 2017.

Fat cells called adipocytes are normally found in the skin, but they're lost when wounds heal as scars. The most common cells found in healing wounds are myofibroblasts, which were thought to only form a scar. Scar tissue also does not have any hair follicles associated with it, which is another factor that gives it an abnormal appearance from the rest of the skin. Researchers used these characteristics as the basis for their work - changing the already present myofibroblasts into that do not cause scarring.

"Essentially, we can manipulate wound healing so that it leads to skin regeneration rather than scarring," said George Cotsarelis, MD, the chair of the Department of Dermatology and the Milton Bixler Hartzell Professor of Dermatology at Penn, and the principal investigator of the project. "The secret is to regenerate hair follicles first. After that, the fat will regenerate in response to the signals from those follicles."

The study showed hair and fat develop separately but not independently. Hair follicles form first, and the Cotsarelis lab previously discovered factors necessary for their formation. Now they've discovered additional factors actually produced by the regenerating to convert the surrounding myofibroblasts to regenerate as fat instead of forming a scar. That fat will not form without the new hairs, but once it does, the new cells are indistinguishable from the pre-existing fat cells, giving the healed wound a natural look instead of leaving a scar. As they examined the question of what was sending the signal from the hair to the fat cells, researchers identified a factor called Bone Morphogenetic Protein (BMP). It instructs the myofibroblasts to become fat. This signaling was groundbreaking on its own, as it changed what was previously known about myofibroblasts.

"Typically, myofibroblasts were thought to be incapable of becoming a different type of cell," Cotsarelis said. "But our work shows we have the ability to influence these cells, and that they can be efficiently and stably converted into adipocytes." This was shown in both the mouse and in human keloid cells grown in culture.

"The findings show we have a window of opportunity after wounding to influence the tissue to regenerate rather than scar," said the study's lead author Maksim Plikus, PhD, an assistant professor of Developmental and Cell Biology at the University of California, Irvine. Plikus began this research as a postdoctoral fellow in the Cotsarelis Laboratory at Penn, and the two institutions have continued to collaborate.

The progression of the wound during healing when hair follicles are present. Credit: Penn Medicine

These discoveries have the potential to be revolutionary in the field of dermatology. The first and most obvious use would be to develop a therapy that signals myofibroblasts to convert into adipocytes—helping wounds heal without scarring.

"It's highly desirable from a clinical standpoint, but right now it's an unmet need," Cotsarelis said.

But the increase of fat cells in tissue can also be helpful for more than just wounds. Adipocyte loss is a common complication of other conditions, especially treatments for HIV, and right now there is no efficient strategy for treatment. The cells are also lost naturally because of the aging process, especially in the face, which leads to permanent, deep wrinkles, something anti-aging treatments can't fix in a cosmetically satisfactory way.

"Our findings can potentially move us toward a new strategy to regenerate adipocytes in wrinkled skin, which could lead us to brand new anti-aging treatments," Cotsarelis said.

The Cotsarelis Lab is now focusing on the mechanisms that promote skin regeneration, especially with respect to hair follicle regeneration.

The Plikus Laboratory is focusing on other aspects of cell reprogramming in skin . Researchers there are examining the role of other signaling factory beyond BMP as well as conducting further studies using human cells and human .

Explore further: Growth factor responsible for triggering hair follicle generation during wound healing identified

More information: "Regeneration of fat cells from myofibroblasts during wound healing," Science, science.sciencemag.org/lookup/ … 1126/science.aai8792

Related Stories

Growth factor responsible for triggering hair follicle generation during wound healing identified

June 2, 2013
Researchers in the Perelman School of Medicine at the University of Pennsylvania have determined the role of a key growth factor, found in skin cells of limited quantities in humans, which helps hair follicles form and regenerate ...

Researchers identify drug candidate for skin, hair regeneration in scarred burn and trauma victims

August 6, 2015
Johns Hopkins researchers have identified a novel cell signaling pathway in mice through which mammals—presumably including people—can regenerate hair follicles and skin while healing from wounds.

Study reveals how to regenerate mouse ears without a scar

November 2, 2015
In contrast to amphibian tissue regeneration, traumatic injuries in mammals typically heal with a fibrous scar. Researchers discovered that some strains of mice heal without a scar, by disrupting a protein, called Sdf1, that ...

Recommended for you

New inflammation inhibitor discovered

November 16, 2018
A multidisciplinary team of researchers led from Karolinska Institutet in Sweden have developed an anti-inflammatory drug molecule with a new mechanism of action. By inhibiting a certain protein, the researchers were able ...

Gut hormone and brown fat interact to tell the brain it's time to stop eating

November 15, 2018
Researchers from Germany and Finland have shown that so-called "brown fat" interacts with the gut hormone secretin in mice to relay nutritional signals about fullness to the brain during a meal. The study, appearing November ...

Brain, muscle cells found lurking in kidney organoids grown in lab

November 15, 2018
Scientists hoping to develop better treatments for kidney disease have turned their attention to growing clusters of kidney cells in the lab. One day, so-called organoids—grown from human stem cells—may help repair damaged ...

How the Tasmanian devil inspired researchers to create 'safe cell' therapies

November 15, 2018
A contagious facial cancer that has ravaged Tasmanian devils in southern Australia isn't the first place one would look to find the key to advancing cell therapies in humans.

Researchers discover important connection between cells in the liver

November 15, 2018
University of Minnesota Medical School researchers have made a discovery which could lead to a new way of thinking about how disease pathogenesis in the liver is regulated, which is important for understanding the condition ...

Precision neuroengineering enables reproduction of complex brain-like functions in vitro

November 14, 2018
One of the most important and surprising traits of the brain is its ability to dynamically reconfigure the connections to process and respond properly to stimuli. Researchers from Tohoku University (Sendai, Japan) and the ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.