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In a new study involving three volunteers, skin scars started to behave more like uninjured skin after being treated with hair follicle transplants. The scarred skin harbored new cells and blood vessels, remodeled collagen to restore healthy patterns, and even expressed genes found in healthy, unscarred skin.
The findings could lead to better treatments for scars both on the skin and inside the body, giving hope to patients with extensive scarring, which can impair organ function and lead to disability.
After healing, the skin never fully regains its pre-wound functions and so far all scar remodeling efforts have yielded poor results. Our findings lay the groundwork for exciting new therapies that can rejuvenate even mature scars and restore healthy skin function.”
Dr Claire Higgins, lead author, Imperial Department of Bioengineering
The research is published today in npj Regenerative Medicine.
hope in the hair
Scar tissue in the skin lacks hair, sweat glands, blood vessels, and nerves, which are vital for regulating body temperature and sensing pain and other sensations. Scars can also impede movement and potentially cause discomfort and emotional distress.
Compared to scar tissue, healthy skin undergoes constant remodeling by the hair follicle. Hairy skin heals faster and there are fewer scars than non-hairy skin and hair grafts. Inspired by this, the researchers hypothesized that transplanting growing hair follicles into scar tissue could prompt scars to reshape.
To test their hypothesis, the Imperial researchers worked with Dr. Francisco Jiménez, chief hair transplant surgeon at Mediteknia Clinic and associate research professor at Fernando Pessoa Canarias University, Gran Canaria, Spain. . They transplanted hair follicles into the mature scalp scars of three participants in 2017. The researchers selected the most common type of scar, called normotrophic scars, which typically form after surgery.
They took and microscopically photographed 3mm-thick biopsies of the scars just before the transplant, and again at two, four and six months later.
The researchers found that the follicles inspired profound architectural and genetic changes in the scars towards a profile of healthy, uninjured skin.
Dr Jiménez said: “Around 100 million people a year acquire scars in high-income countries alone, mostly from surgeries. The global incidence of scars is much higher and includes extensive scars formed after burns and traumatic injuries. Our work opens up new avenues for treating scars and may even change our approach to preventing them.”
Skin Architects
After transplantation, the follicles continued to produce hair and induced restoration through the skin layers.
Scarring causes the outermost layer of skin, the epidermis, to thin, making it vulnerable to tearing. Six months after the transplant, the epidermis had doubled in thickness alongside increased cell growth, bringing it to about the same thickness as uninjured skin.
The next layer of skin, the dermis, is populated by connective tissue, blood vessels, sweat glands, nerves, and hair follicles. Maturing scars leave the dermis with fewer cells and blood vessels, but after transplantation the number of cells had doubled at six months and the number of vessels had reached near healthy skin levels at four months. This demonstrated that the follicles inspired the growth of new cells and blood vessels in the scars, which are unable to do so unaided.
Scarring also increases the density of collagen fibers – a major structural protein in skin – causing them to line up in such a way that scar tissue is stiffer than healthy tissue. Hair transplants reduced fiber density, allowing them to form a healthier “basket weave” pattern, which reduced stiffness – a key contributor to tears and discomfort.
The authors also found that after transplantation, the scars expressed 719 genes differently from before. Genes that promote cell and blood vessel growth were expressed more, while genes that promote scar formation processes were expressed less.
Multi-pronged approach
Researchers aren’t sure exactly how the transplants facilitated such a change. In their study, the presence of a hair follicle in the scar was cosmetically acceptable because the scars were on the scalp. They are now working to uncover the underlying mechanisms so they can develop therapies that transform scar tissue into healthy skin, without requiring the transplantation of a hair follicle and the growth of a hair fiber. They can then test their findings on non-hairy skin or on organs like the heart, which can be scarred after a heart attack, and the liver, which can be scarred through fatty liver and cirrhosis.
Dr Higgins said: “This work has obvious applications for restoring people’s confidence, but our approach goes beyond cosmetics because scar tissue can cause problems in all our organs.
“While current scar treatments like growth factors focus on single contributors to scarring, our new approach addresses multiple aspects, as the hair follicle likely provides multiple growth factors at once that remodel scar tissue. This lends further support to the use of treatments like hair transplantation that alter the very architecture and genetic expression of scars to restore function.”
This work was funded by the Medical Research Council and the Engineering and Physical Sciences Research Council (part of UKRI).
Source:
Journal reference:
Plotczyk, M. et al. (2023) Anagen hair follicles transplanted into mature human scars remodel fibrotic tissue. npj regenerative medicine. doi.org/10.1038/s41536-022-00270-3.
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