Significant role for hair follicle stem cells in blister healing


A fluorescent micrograph of a cross-section through an epidermal blister on mice skin. The epidermis (green) is detached from the other layers (magenta) of skin tissue (Yu Fujimura, et al. EMBO Reports. June 4, 2021).

New research has revealed that the healing of skin blisters is driven in part by hair follicle stem cells. This process delays the development of the hair follicles involved.


“Our findings of the healing processes pave the way for tailored therapeutic interventions for epidermolysis bullosa, pemphigoid diseases and other blistering diseases,” said researcher Dr. Ken Natsuga in a press release. Dr. Natsuga is an associate professor at the Graduate School of Medicine at Hokkaido University in Sapporo, Japan.


The investigators artificially induced epidermal detachment—skin blisters—in animal models, then investigated how the skin healed. Their monitoring included evaluating gene expressions and cell proliferation, as well as tracing cell lineages.


They found that hair follicle stem cells played a significant role in healing the blisters, and were responsible for healing subepidermal blisters from the base of the wound. The wound-healing activity of these stem cells was associated with a delay in the growth of hair follicles in the regenerating skin.


Hair follicle stem cells contribute to blister healing. In uninjured skin, the follicles give rise to hair. When the skin blisters, the hair follicles contribute to healing at the cost of delaying their growth (Yu Fujimura, et al. EMBO Reports. June 4, 2021).

When the investigators reduced the number of hair follicle stem cells, they found that interfollicular epidermal stem cells could contribute to healing the blister but worked inward from the blister margins.


The shapes of keratinocytes also affected blister healing, but the researchers were not able to determine the mechanism by which the keratinocyte shapes influenced healing.


These findings could lead to new possibilities for understanding skin blistering in humans, according to the researchers, potentially including new therapies.


Two aspects of the skin and how they may contribute to wound healing were not explored in this study and will be the focus of future research, the authors say. These include the role of mesenchymal cells and the role of sweat glands.

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