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Significance: Hair follicles are complex miniorgans that reside in the dermal layer of the skin. When the skin is wounded, epidermal stem cells in the hair follicle activate and start migrating into the wound site, differentiating into epidermal cells. and contributing to the reepithelialization of the wound. The hair follicles represent the deepest epidermal elements in the skin, which are extremely beneficial in partial-thickness burns and abrasions where the skin can regenerate from the hair follicles. Recent Advances: Advanced animal models have demonstrated that the contribution of epidermal stem cells in the hair follicle bulge and isthmus regions is important for wound healing. In addition, several clinical studies have shown successful harvesting and transplantation of hair follicles as a treatment modality to accelerate wound healing. Critical Issues: Deep and large wounds require hospitalization and, without exception, surgical treatment. Harvesting and direct transplantation of hair follicles could provide a great source of autologous epidermal stem cells for wound healing. The procedure can be done in an outpatient setting, quickly and without creating a large donor site wound. Future Directions: Transplantation of hair follicles in a combination with novel biomaterials could provide advantageous treatment possibilities for both chronic wounds and burns. There is a substantial amount of molecular signaling data available on the role of hair follicles during wound repair, but almost all the data are derived from rodent models, and thus, more information from large animals and most importantly from humans would be beneficial and help to advance this promising treatment further.

Local transplantation of stem cells has therapeutic effects on skin damage but cannot provide satisfactory wound healing. Studies on the mechanisms underlying the therapeutic effects of stem cells on skin wound healing will be needed. Hence, in the present study, we explored the role of Caveolin-1 in epidermal stem cells (EpiSCs) in the modulation of wound healing. We first isolated EpiSCs from mouse skin tissues and established stable EpiSCs with overexpression of Caveolin-1 using a lentiviral construct. We then evaluated the epidermal growth factor (EGF)-induced cell proliferation ability using cell counting Kit-8 (CCK-8) assay and assessed EpiSC pluripotency by examining Nanog mRNA levels in EpiSCs. Furthermore, we treated mice with skin burn injury using EpiSCs with overexpression of Caveolin-1. Histological examinations were conducted to evaluate re-epithelialization, wound scores, cell proliferation and capillary density in wounds. We found that overexpression of Caveolin-1 in EpiSCs promoted EGF-induced cell proliferation ability and increased wound closure in a mouse model of skin burn injury. Histological evaluation demonstrated that overexpression of Caveolin-1 in EpiSCs promoted re-epithelialization in wounds, enhanced cellularity, and increased vasculature, as well as increased wound scores. Taken together, our results suggested that Caveolin-1 expression in the EpiSCs play a critical role in the regulation of EpiSC proliferation ability and alteration of EpiSC proliferation ability may be an effective approach in promoting EpiSC-based therapy in skin wound healing., (Copyright © 2018 Elsevier Inc. All rights reserved.)

During the process of skin regeneration following a skin injury, de novo hair follicle regeneration is initiated after wounding; however, these regenerated hairs are mostly unpigmented. The activation of epidermal melanocyte stem cells and their differentiation into regenerating hair follicles have been shown to be necessary for the pigmented hair regeneration after wounding. To determine the role of flavonoids in the regeneration of pigmented hairs, we applied the candidate flavonoids to the regenerating hair follicles after wounding and identified the flavonoid species that maximally induced pigmented hair regeneration. Flavonoids with two OH groups in the B-ring, such as sterubin, luteolin, and hydroxygenkwanin, showed promising effects in regenerating black pigmented hairs, while those with one OH group in the B-ring showed no significant change. Thus, flavonoids with two OH groups in their B-ring could be studied further as potential wound healing agents with the ability to regenerate pigmented hair.

Large excisional wounds in mice prominently regenerate new hair follicles (HFs) and fat, yet humans are deficient for this regenerative behavior. Currently, wound-induced regeneration remains a clinically desirable, but only partially understood phenomenon. We show that large excisional wounds in rats across seven strains fail to regenerate new HFs. We compared wound transcriptomes between mice and rats at the time of scab detachment, which coincides with the onset of HF regeneration in mice. In both species, wound dermis and epidermis share core dermal and epidermal transcriptional programs, respectively, yet prominent interspecies differences exist. Compared with mice, rat epidermis expresses distinct transcriptional and epigenetic factors, markers of epidermal repair, hyperplasia, and inflammation, and lower levels of WNT signaling effectors and regulators. When recombined on the surface of excisional wounds with vibrissa dermal papillae, partial-thickness skin grafts containing distal pelage HF segments, but not interfollicular epidermis, readily regenerated new vibrissa-like HFs. Together, our findings establish rats as a nonregenerating rodent model for excisional wound healing and suggest that low epidermal competence and associated transcriptional profile may contribute to its regenerative deficiency. Future comparison between rat and mouse may lend further insight into the mechanism of wounding-induced regeneration and causes for its deficit., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)