Epithelial hair follicle stem cells (eHFSCs) are required to generate, maintain and renew the continuously cycling hair follicle (HF), supply cells that produce the keratinized hair shaft and aid in the reepithelialization of injured skin. Therefore, their study is biologically and clinically important, from alopecia to carcinogenesis and regenerative medicine. However, human eHFSCs remain ill defined compared to their murine counterparts, and it is unclear which murine eHFSC markers really apply to the human HF. We address this by reviewing current concepts on human eHFSC biology, their immediate progeny and their molecular markers, focusing on Keratin 15 and 19, CD200, CD34, PHLDA1, and EpCAM/Ber-EP4. After delineating how human eHFSCs may be selectively targeted experimentally, we close by defining as yet unmet key challenges in human eHFSC research. The ultimate goal is to transfer emerging concepts from murine epithelial stem cell biology to human HF physiology and pathology.

Inflammation-associated, irreversible damage to epithelial stem cells (eSCs) of the hair follicle in their immunologically privileged niche lies at the heart of scarring alopecia, which causes permanent difficult-to-treat hair loss. We propose that the two most common and closely related forms, lichen planopilaris (LPP) and frontal fibrosing alopecia (FFA), provide excellent model diseases for studying the biology and pathology of adult human eSCs in an easily accessible human mini-organ. Emphasising the critical roles for interferon (IFN)-γ and peroxisome proliferator-activated receptor (PPAR)-γ-mediated signalling in immune privilege (IP) collapse and epithelial-mesenchymal transition (EMT) of these eSCs respectively, we argue that these pathways deserve therapeutic targeting in the future management of LPP/FFA and other eSC diseases associated with IP collapse and EMT.

Epithelial-to-mesenchymal transition (EMT) is critical for embryonic development and wound healing, and occurs in fibrotic disease and carcinoma. Here, we show that EMT also occurs within the bulge, the epithelial stem cell (eSC) niche of human scalp hair follicles, during the inflammatory permanent alopecia, lichen planopilaris. We show that a molecular EMT signature can be experimentally induced in healthy human eSCs in situ by antagonizing E-cadherin, combined with transforming growth factor-β1, epidermal growth factor, and IFN-γ administration, which to our knowledge has not been reported previously. Moreover, induction of EMT within primary human eSCs can be prevented and even partially reversed ex vivo by peroxisome proliferator-activated receptor-γ agonists, likely through suppression of the transforming growth factor-β signaling pathway. Furthermore, we show that peroxisome proliferator-activated receptor-γ agonists also attenuates the EMT signature even in lesional lichen planopilaris hair follicles ex vivo. We introduce lichen planopilaris as a model disease for pathological EMT in human adult eSCs, report a preclinical assay for therapeutically manipulating eSC EMT within a healthy human (mini-)organ, and show that peroxisome proliferator-activated receptor-γ agonists are promising agents for suppressing and partially reversing EMT in human hair follicles eSCs ex vivo, including in lichen planopilaris.

Only anagen human hair follicles show CD34 immunoreactivity. CD34 and CK15 recognize different types of cells or cells at different stages of differentiation.

Background  Frontal fibrosing alopecia (FFA) is an acquired scarring alopecia currently considered a clinical variant of lichen planopilaris (LPP). Our purpose was to examine the clinicopathological features of FFA. In addition, we investigated the similarities and differences between FFA and LPP. Methods  Biopsies from the scalp lesions of eight patients with FFA and eight patients with LPP were microscopically analyzed. Two cases of FFA and four cases of LPP were studied using direct immunofluorescence. Results  In spite of the completely different clinical characteristics of FFA and LPP patients, the histopathological findings for the two entities were similar. Common microscopic findings for both FFA and LPP included an inflammatory lymphocytic infiltrate involving the isthmus and infundibulum of the hair follicles, the presence of apoptotic cells in the external root sheath, and a concentric fibrosis surrounding the hair follicles that resulted in their destruction with subsequent scarring alopecia. Biopsies taken from FFA patients showed less follicular inflammation and more apoptotic cells than those from LPP patients. In some cases of LPP, the inflammatory infiltrate involved the interfollicular epidermis, a finding never present in our FFA cases. Direct immunofluorescence was negative in the two cases of FFA studied and showed deposits of immunoglobulins and/or complement in two of the four LPP cases examined. Conclusions  The characteristic findings for FFA were more prominent apoptosis and less inflammation than found in LPP, along with spared interfollicular epidermis. FFA cases showed a rather characteristic histopathological pattern, although we could not find any clear‐cut histological differences between FFA and LPP.

The characteristic findings for FFA were more prominent apoptosis and less inflammation than found in LPP, along with spared interfollicular epidermis. FFA cases showed a rather characteristic histopathological pattern, although we could not find any clear-cut histological differences between FFA and LPP.

Observational studies of multilevel data to estimate treatment effects must consider both the nonrandom treatment assignment mechanism and the clustered structure of the data. We present an approach for implementation of four propensity score (PS) methods with multilevel data involving creation of weights and three types of weight scaling (normalized, cluster-normalized and effective), followed by estimation of multilevel models with the multilevel pseudo-maximum likelihood estimation method. Using a Monte Carlo simulation study, we found that the multilevel model provided unbiased estimates of the Average Treatment Effect on the Treated (ATT) and its standard error across manipulated conditions and combinations of PS model, PS method, and type of weight scaling. Estimates of between-cluster variances of the ATT were biased, but improved as cluster sizes increased. We provide a step-by-step demonstration of how to combine PS methods and multilevel modeling to estimate treatment effects using multilevel data from the Early Childhood Longitudinal Study-Kindergarten Cohort (ECLS-K).

Hair restoration is a highly sophisticated subspecialty that offers significant relief to patients with hair loss. An improved understanding of the aesthetics of hair loss and cosmetic hair restoration, hair anatomy and physiology, and the development of microvascular surgical instrumentation has revolutionized the approach to surgical hair restoration since the original description. Additional elements that contribute to the current state of the art in hair restoration include graft size, site creation, packing density, and medical control of hair loss. The results of hair restoration are natural in appearance and are provided with a very high level of patient satisfaction and safety. This aspect of cosmetic surgery is a very welcome addition to a traditional aesthetic practice and serves as a tremendous source for internal cross-referral. The future of hair restoration surgery is centered on minimal-incision surgery as well as cell-based therapies.