New insights into how skin can regenerate after severe burns
Findings provide basis for developing drugs to improve healing in
severely damaged skin

Date:
August 19, 2020
Source:
University of Calgary
Summary:
New research has made an exciting leap forward in understanding
how skin heals, which could lead to drug treatments to vastly
improve wound healing.



FULL STORY ========================================================================== People who suffer severe burns or extensive skin injuries are often
left to live with extreme scarring, disfigurement, and skin that feels chronically tight and itchy. That's because the body's healing processes
have evolved to focus on preventing infection by quickly closing up
wounds, rather than regenerating or restoring normal skin tissue.


==========================================================================
New research led by Dr. Jeff Biernaskie, PhD, has made an exciting
leap forward in understanding how skin heals, which could lead to drug treatments to vastly improve wound healing. The study, published in the scientific journal Cell Stem Cell, was co-led by Dr. Sepideh Abbasi, PhD, Sarthak Sinha, MD/PhD candidate and Dr. Elodie Labit, PhD, postdoctoral
fellow.

"We identified a specific population of progenitor cells that reside
within the dermis, the deep connective tissue of the skin. Progenitor
cells, are unique in that they are able to undergo cell division and
generate many new cells to either maintain or repair tissues. Following
injury, these dermal progenitors become activated, proliferate and
then migrate into the wound where they generate nearly all of the new
tissue that will fill the wound, both scar and regenerated tissue," says Biernaskie, professor of stem cell biology in the University of Calgary
Faculty of Veterinary Medicine (UCVM), and the Calgary Firefighters Burn Treatment Society Chair in Skin Regeneration and Wound Healing.

Biernaskie's intensive study, five years in the making, offers new
knowledge on why certain dermal cells are able to regenerate new
skin, rather than disfiguring scar tissue. Using cutting-edge genomics techniques to profile thousands of individual cells at different times
after injury, the research team compared scar-forming versus regenerative
zones within skin wounds.

"Remarkably, we found that although these cells come from the same
cellular origin, different microenvironments within the wound activate
entirely different sets of genes. Meaning, the signals found within 'regenerative zones' of the wound promote re-activation of genes that are typically engaged during skin development. Whereas, in scar-forming zones
these pro-regenerative programs are absent or suppressed and scar-forming programs dominate." Working with these findings, the researchers then
showed it's possible to modify the genetic programs that govern skin regeneration.

"What we've shown is that you can alter the wound environment with
drugs, or modify the genetics of these progenitor cells directly, and
both are sufficient to change their behaviour during wound healing. And
that can have really quite impressive effects on healing that includes regeneration of new hair follicles, glands and fat within the wounded
skin," says Biernaskie.

This research offers critical insights into the molecular signals that
drive scar formation during wound healing and it identifies a number
of genetic signals that are able to overcome fibrosis and promote true regeneration of adult skin.

"This proof of principle is really important, because it suggests that
the adult wound-responsive cells do in fact harbor a latent regenerative capacity, it just simply needs to be unmasked," says Biernaskie. "Now,
we are actively looking for additional pathways that may be involved. Our
hope is to develop a cocktail of drugs that we could safely administer
in humans and animals to entirely prevent genetic programs that initiate
scar formation in order to greatly improve the quality of skin healing."
The study was funded by the Canadian Institutes of Health Research and
the Calgary Firefighters Burn Treatment Society.


========================================================================== Story Source: Materials provided by University_of_Calgary. Original
written by Collene Ferguson. Note: Content may be edited for style
and length.


========================================================================== Journal Reference:
1. Sepideh Abbasi, Sarthak Sinha, Elodie Labit, Nicole L. Rosin,
Grace Yoon,
Waleed Rahmani, Arzina Jaffer, Nilesh Sharma, Andrew Hagner, Prajay
Shah, Rohit Arora, Jessica Yoon, Anowara Islam, Aya Uchida, Chih
Kai Chang, Jo Anne Stratton, R. Wilder Scott, Fabio M.V. Rossi,
T. Michael Underhill, Jeff Biernaskie. Distinct Regulatory
Programs Control the Latent Regenerative Potential of Dermal
Fibroblasts during Wound Healing. Cell Stem Cell, 2020; DOI:
10.1016/j.stem.2020.07.008 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/08/200819120710.htm

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