mTORC1 activity negatively regulates human hair follicle growth and pigmentation.

Dysregulation of the activity of the mechanistic target of rapamycin complex 1 (mTORC1) is commonly linked to aging, cancer, and genetic disorders such as tuberous sclerosis (TS), a rare neurodevelopmental multisystemic disease characterized by benign tumors, seizures, and intellectual disability. Although patches of white hair on the scalp (poliosis) are considered as early signs of TS, the underlying molecular mechanisms and potential involvement of mTORC1 in hair depigmentation remain unclear. Here, we have used healthy, organ-cultured human scalp hair follicles (HFs) to interrogate the role of mTORC1 in a prototypic human (mini-)organ. Gray/white HFs exhibit high mTORC1 activity, while mTORC1 inhibition by rapamycin stimulated HF growth and pigmentation, even in gray/white HFs that still contained some surviving melanocytes. Mechanistically, this occurred via increased intrafollicular production of the melanotropic hormone, α-MSH. In contrast, knockdown of intrafollicular TSC2, a negative regulator of mTORC1, significantly reduced HF pigmentation. Our findings introduce mTORC1 activity as an important negative regulator of human HF growth and pigmentation and suggest that pharmacological mTORC1 inhibition could become a novel strategy in the management of hair loss and depigmentation disorders.

Interleukin-15 is a hair follicle immune privilege guardian.

The autoimmunity-promoting cytokine, Interleukin-15 (IL-15), is often claimed to be a key pathogenic cytokine in alopecia areata (AA). Yet, rhIL-15 promotes human hair follicle (HF) growth ex vivo. We have asked whether the expression of IL-15 and its receptor (IL-15R) isoforms is altered in human AA and how IL-15 impacts on human HF immune privilege (HF-IP) in the presence/absence of interferon-γ (IFNγ), the well-documented key AA-pathogenic cytokine, as well as on hair regrowth after experimental AA induction in vivo. Quantitative immunohistomorphometry showed the number of perifollicular IL-15+ T cells in AA skin biopsies to be significantly increased compared to healthy control skin, while IL-15, IL-15Rα, and IL-15Rγ protein expression within the hair bulb were significantly down-regulated in AA HFs. In organ-cultured human scalp HFs, rhIL-15 significantly reduced hair bulb expression of MICA, the key "danger" signal in AA pathogenesis, and increased production of the HF-IP guardian, α-MSH. Crucially, ex vivo, rhIL-15 prevented IFNγ-induced HF-IP collapse, restored a collapsed HF-IP by IL-15Rα-dependent signaling (as documented by IL-15Rα-silencing), and protected AA-preventive immunoinhibitory iNKT10 cells from IFNγ-induced apoptosis. rhIL-15 even promoted hair regrowth after experimental AA induction in human scalp skin xenotransplants on SCID/beige mice in vivo. Our data introduce IL-15 as a novel, functionally important HF-IP guardian whose signaling is constitutively defective in scalp HFs of AA patients. Our data suggest that selective stimulation of intrafollicular IL-15Rα signaling could become a novel therapeutic approach in AA management, while blocking it pharmacologically may hinder both HF-IP restoration and hair re-growth and may thus make HFs more vulnerable to AA relapse.

Microneedling in All Skin Types: A Review.

INTRODUCTION: Microneedling procedures are growing in popularity for a wide variety of skin conditions. This paper comprehensively reviews the medical literature regarding skin needling efficacy and safety in all skin types and in multiple dermatologic conditions.

METHODS: A PubMed literature search was conducted in all languages without restriction and bibliographies of relevant articles reviewed. Search terms included: "microneedling," "percutaneous collagen induction," "needling," "skin needling," and "dermaroller."

RESULTS: Microneedling is most commonly used for acne scars and cosmetic rejuvenation, however, treatment benefit has also been seen in varicella scars, burn scars, keloids, acne, alopecia, and periorbital melanosis, and has improved flap and graft survival, and enhanced transdermal delivery of topical products. Side effects were mild and self-limited, with few reports of post-inflammatory hyperpigmentation, and isolated reports of tram tracking, facial allergic granuloma, and systemic hypersensitivity.

DISCUSS: Microneedling represents a safe, cost-effective, and efficacious treatment option for a variety of dermatologic conditions in all skin types. More double-blinded, randomized, controlled trials are required to make more definitive conclusions.

J Drugs Dermatol. 2017;16(4):308-314.

Hairline-Lowering Surgery.

As an alternative to hair transplantation for lowering the overly high hairline, hairline-lowering/forehead-reduction surgery has several advantages, including unsurpassed density and immediate results. Appropriate candidates for this surgery must have a stable frontal hairline (thus excluding most men) and a fairly to very mobile scalp that will permit sufficient advancement to warrant this more "invasive" approach. The main objective of this surgery is the lowering of the hairline. The authors' surgical approach, which was developed over the performance of more than 90 of these procedures and produces consistent results with low rates of complications, is described.

Follicular Unit Excision: Current Practice and Future Developments.

Hair transplantation, or hair restoration surgery (HRS) remains the only method to consistently restore hair in those experiencing pattern hair loss as well as hair loss from most other causes. HRS has been significantly improved with the development of follicular unit extraction, later renamed follicular unit excision, or FUE. This allows the surgeon to harvest grafts from the donor area without leaving a scar. FUE can also be used to harvest grafts from other areas of the body. When performed properly using the most technically advanced devices, the transection of the grafts with FUE remains under 4%.

Mesenchymal Stem Cells and Stromal Vascular Fraction for Hair Loss: Current Status.

The current state of the applicability of cell therapy for the treatment of various conditions of hair loss reveals a promising and potentially effective role. Further research, based on published work to date, is indicated to further explore the potential roles of autologous fat grafting, mesenchymal stem cells, and stromal vascular fraction therapy. The authors' evolving experience matches these promising scientific findings.