Manipulating the Wound Healing Process to Prevent Scarring

While there are some engineered mammalian lineages that can heal small wounds without scarring, further investigations of the biochemistry involved have yet to lead to a robust clinical treatment. Other lines of research are starting to look more promising, however. Here researchers demonstrate early implementations of a methodology that may prove to be the basis for a practical therapy to reduce scar tissue formation in wound healing:

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 fat cells that do not cause scarring. "Essentially, we can manipulate wound healing so that it leads to skin regeneration rather than scarring. 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 researchers previously discovered factors necessary for their formation. Now they've discovered additional factors actually produced by the regenerating hair follicle 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, 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. 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 also has potential cosmetic applications - less wrinkly facial skin and perhaps hair regrowth for baldness:

"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."

Posted by: Jim at January 6th, 2017 8:47 AM

@ Jim : I believe those applications would tremendously help improve the public recognition and funding of rejuvenation research.

Posted by: Spede at January 6th, 2017 9:15 AM

@Spede - Well it might be a long way off testing in humans, unless some wild person like Liz Parish starts self treating with BMP down in Colombia.

You probably could measure before and after fat in the facial skin via biopsy. Also if she (or whoever) started looking a bit younger, that might intensify interest. On the other hand you might need to get rid of a bunch of other damage (Glucosepane, senescent cells etc) to make any real difference in appearance.

Posted by: Jim at January 6th, 2017 10:36 AM

Scarless wound healing would provide a way of getting rid of the aging damage present in the skin; wound the skin, thereby getting rid of any damaged collagen in the wound area, and when it heals scarlessly it will freshly synthesise new, undamaged collagen. It would be a very painful and slow procedure, but some would be willing to go through with it and would genuinely produce rejuvenated skin (although, it is possible that it would not appear completely rejuvenated due to the effects of the aging damage present in the rest of the body through aberrant signalling and the like).

Posted by: Arcanyn at January 7th, 2017 2:24 AM

It might depend on how much wounding is needed. If simple dermal abrasion is needed (eg face scrub), plus application of appropriate signals, then it might be quite workable. If it needs constant dolorous wounding then probably not, except as treatment for serious wounds, burns or other serious afflictions.

Posted by: Hervé Musseau at January 8th, 2017 9:21 AM

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