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Review
. 2015 Jan 5;5(1):a023267.
doi: 10.1101/cshperspect.a023267.

Wound healing and skin regeneration

Makoto Takeo  1 , Wendy Lee  1 , Mayumi Ito  1
Affiliations
Review

Wound healing and skin regeneration

Makoto Takeo et al. Cold Spring Harb Perspect Med. .

Abstract

The skin is a complex organ consisting of the epidermis, dermis, and skin appendages, including the hair follicle and sebaceous gland. Wound healing in adult mammals results in scar formation without any skin appendages. Studies have reported remarkable examples of scarless healing in fetal skin and appendage regeneration in adult skin following the infliction of large wounds. The models used in these studies have offered a new platform for investigations of the cellular and molecular mechanisms underlying wound healing and skin regeneration in mammals. In this article, we will focus on the contribution of skin appendages to wound healing and, conversely, skin appendage regeneration following injuries.

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Figures

Figure 1.
Figure 1.
Contributions of hair follicle stem cells to re-epithelialization. (A) Schematic illustration of bulge stem cell markers that contribute to re-epithelialization. (B) Lineage tracing of K15+ hair follicle stem cells after excisional wound using K15-LacZ mice. LacZ-positive cells were not found in IFE at 2 d after wounding (right panel). At 5 d, LacZ+ cells start to migrate from hair follicle to wound center (middle panel). At 8 d after wounding, re-epithelialization is completed and about 26% of re-epithelialized cells are lacZ+ (left panel). (From Ito et al. 2005; reprinted, with permission.)
Figure 2.
Figure 2.
Schematic illustration of molecular mechanisms during hair follicle morphogenesis (top) and neogenesis (bottom).
Figure 3.
Figure 3.
Contribution of hair follicle–derived melanocytes to hair follicle neogenesis. (A–C) Hair regeneration from newly formed hair follicle in wound area. Note that almost all hair lack pigment. (D) Distribution of hair follicle derived melanocytes in the wound in Dct-LacZ reporter mice in which melanocyte including McSCs are labeled with LacZ. Most of the epidermal melanocytes are restricted to the wound periphery, and only a few melanocytes are found in the center of wound where hair follicle neogenesis occurs (red dashed line). (E) Occasional pigmented hair regeneration. (F) Whole mount view of newly formed hair follicle that produce pigmented hair. Note the presence of McSCs in the bulge. (G) Schematic illustration of the contribution of hair follicle–derived melanocytes to hair follicle neogenesis. Scale bars, 1 mm. (A–C from Ito et al. 2007; reproduced, with permission; D–G from Chou et al. 2013; reproduced, with permission.)
Figure 4.
Figure 4.
Relationship between nail regeneration and digit regeneration. Alcian blue/alizarin red staining of mouse digit at 5 weeks after distal (A), or proximal (B) amputation. When a digit is amputated at the distal level, both nail and underlying mesenchymal digit bone regenerates A, while neither nail nor digit bone regenerates from proximal amputation B. (Panel B is from Takeo et al. 2013; reproduced, with permission.)
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