Adipose transcriptome in the scalp of androgenetic alopecia.

Previous studies have shown how adipocytes can modulate the activity of hair follicle stem cells. However, the role of adipocytes in the pathogenesis of androgenetic alopecia (AGA) remains unknown. We aimed to determine signaling pathways related to the adipose tissue changes in the human scalp with AGA through RNA-seq analysis. RNA was isolated from the adipose tissues derived from the bald (frontal) and normal (occipital) scalps of male patients with AGA (n = 4). The pooled RNA extracts from these samples were subjected to RNA sequencing, followed by differential gene expression and pathway analysis. Our gene expression analysis identified 1,060 differentially expressed genes, including 522 upregulated and 538 downregulated genes in the bald AGA scalp. Biological pathways pertaining to either adipose tissue metabolism or the hair cycle were generated in our pathway analysis. Downregulation of the peroxisome proliferator-activated receptor (PPAR) signaling pathway was noted to be significant in the bald scalp. Expression of adipogenic markers (e.g., PPARG, FABP4, PLN1, and ADIPOQ) was also decreased in the bald site. These findings imply that adipogenesis becomes downregulated in AGA, specifically within the bald scalp adipose. Our results lead to the hypothesis that PPARγ-mediated adipogenesis in the scalp adipose, via crosstalk with signaling pathways involved in hair cycling, might play a role in AGA.

Stress-induced premature senescence of dermal papilla cells compromises hair follicle epithelial-mesenchymal interaction.

BACKGROUND: Hair follicle is miniorgan constituted by keratinocytes and its distinctive mesenchyme of dermal papilla. Its aging is characterized by organ atrophy and impaired stem cell activation and differentiation. The contribution of dermal papilla to hair follicle aging change is not well understood. OBJECTIVE: This work was aimed at exploring the possible role of premature dermal papilla senescence in the pathogenesis of hair follicle aging. METHODS: Dermal papilla cells were challenged with H2O2 to induce premature senescence and the proliferation, apoptosis, gene expression and protein secretion were characterized. Its effect on epithelial-mesenchymal interaction was analyzed by co-culture in vitro and implantation of protein-coated beads in vivo. RESULT: Dermal papilla cells were more resistant to oxidative stress-induced apoptosis than dermal fibroblasts. The surviving dermal papilla cells showed signs of senescence but still preserved key dermal papilla signature gene expression. In addition to the failure to respond to mitogenic stimulation from keratinocytes, they lost the ability to induce hair follicle neogenesis, promoted interfollicular epidermal differentiation, inhibited follicular differentiation and, importantly, suppressed clonal growth of hair follicle stem cells. They produced higher levels of multiple inflammatory cytokines, including IL-6. Functionally, IL-6 inhibited clonal keratinocyte growth in vitro and blocked the transition from telogen to anagen in vivo. CONCLUSION: Stress-induced premature dermal papilla senescence can contribute to hair follicle aging change due to compromised epithelial-mesenchymal interaction.

Quantitative Evaluation of Female Pattern Hair Loss in Chinese Women: A Preliminary Study.

BACKGROUND: The common grading systems for female pattern hair loss (FPHL), such as Ludwig and Savin scales, are subjective to visual inspection. To provide a more objective evaluation of baldness, the authors have developed a method to calculate baldness quantitatively through a computer-aided imaging system (CAIS). OBJECTIVE: To investigate the use of CAIS on Chinese women with FPHL. MATERIALS AND METHODS: Thirty-eight Chinese women with FPHL (Savin Scale I-2 to II-2) were recruited. A total of 215 photographs were taken. The central balding areas (CBAs) were calculated after exposure correction by CAIS for comparison with clinical staging. RESULTS: The average CBA was 9,391.12 mm in all patients, 3,828.84 mm in Type I-2, 5,880.38 mm in I-3, 8,267.44 mm in I-4, 12,999.26 mm in II-1, and 15,979.71 mm in II-2. The values of CBA correlated with clinical staging using Savin scales. A 7.53% difference was found in the calculated CBA by exposure correction. CONCLUSION: The CAIS allows physicians to evaluate the severity of baldness more accurately through quantitative calculation, rather than qualitative visual observation. The values of the CBA measured by the CAIS, used in conjunction with the present grading systems, may be more precise and efficient to evaluate the severity of FPHL.

Scalable production of controllable dermal papilla spheroids on PVA surfaces and the effects of spheroid size on hair follicle regeneration.

Organ size and numbers are vital issues in bioengineering for hair follicle (HF) regeneration. Murine HF dermal papilla (DP) cells are able to induce HF neogenesis when transplanted as aggregates. However, how the preparation of murine and human DP aggregates affects HF inductivity and the size of regenerated HF is yet to be determined. Here we report a scalable method for production of controllable human and rat DP spheroids in general labs for reproducible experiments. Compared with more hydrophobic polyethylene and poly(ethylene-co-vinyl alcohol), DP cells are poorly adhesive to hydrophilic polyvinyl alcohol (PVA). Seeded in PVA-coated 96-welled commercial PCR tube arrays, DP cells quickly aggregate into single spheroids with progressive compaction. Varying seeded cell numbers and culture periods enables us to control the size and cell number of the spheroids. The spheroids obtained have high viability and preserve DP characters. A proof of principle experiment was conducted to examine the size effect on the efficiency and efficacy of HF regeneration. We found that both human and rat DP spheroids are able to induce HF neogenesis and larger DP spheroids exhibit higher HF inductivity. However, the average diameter of regenerated hair fiber did not significantly change with the increasing size of transplanted DP spheroids. The result suggests that an appropriate size of DP spheroid is essential for HF inductivity, but its size cannot be directly translated to a thicker regenerated hair. Our results also have implications on the efficiency and efficacy in the regeneration of other epithelial organs.

Expression of sex-determining genes in the scalp of men with androgenetic alopecia.

BACKGROUND: The regulation of the cutaneous steroidogenesis in patients with androgenetic alopecia remains largely unclear. OBJECTIVE: The purpose of this study was to quantify the expression of the sex-determining genes in different scalp areas. METHODS: Paired scalp specimens from frontal and occipital scalp areas of 10 patients were examined by real-time RT-PCR for mRNA expression and of 40 patients (mean age 34.9 years, range 22-58) by Western blotting for protein analysis. RESULTS: The SOX-9 mRNA was most abundant in the skin, while SF-1 mRNA was sparsely detected. The protein levels of DAX-1, SRY and WT-1 were significantly higher in the bald scalp (p=0.003, 0.004 and 0.03, respectively). Only the SRY expression showed a positive correlation with the baldness severity in Norwood-Hamilton classification (p=0.024). There was no association between patient's age and the protein levels. Immunostaining of SOX-9 was detected in the outer root sheath keratinocytes of hair follicles but not in the dermal papillae. CONCLUSION: Further study on a larger population, including normal subjects and female patients, is needed to confirm the pathogenic role of sex-determining genes in androgenetic alopecia.

Microdermabrasion as a novel tool to enhance drug delivery via the skin: an animal study.

BACKGROUND: Microdermabrasion is a widely performed skin rejuvenation procedure. It can partly ablate and homogenize the stratum corneum (SC) layers. OBJECTIVE: The effect of microdermabrasion treatment on the skin permeation of hydrophilic and lipophilic drugs was examined in this study. METHODS: 5-Fluorouracil (5-FU) and clobetasol 17-propionate were used as the hydrophilic and lipophilic permeants, respectively. In vitro skin delivery using porcine skin and in vivo topical application employing nude mouse as the animal model were both used to examine the effect of microdermabrasion. The vacuum pressures used in this study (15-25 cmHg) were much lower than those used for therapeutic purposes. RESULTS: The 5-FU permeation across microdermabrasion-treated skin was 8- to 24-fold higher than that across intact skin and depended on differences in treatment pressure and duration. An intensity of 15 cmHg for 10 seconds showed the greatest enhancement of 5-FU delivery via the skin. In contrast to the results for 5-FU, microdermabrasion reduced the skin permeation and deposition of topically applied clobetasol. The partitioning effect of clobetasol from the vehicle to the SC may have predominated this result. Microdermabrasion also enhanced the skin delivery of the hydrophilic 5-aminolevulinic acid (ALA). Confocal laser scanning microscopy (CLSM) of microdermabrasion-treated skin revealed intense red fluorescence of ALA-transformed protoporphyrin (PpIX) within the epidermis and upper dermis. CONCLUSIONS: Microdermabrasion can improve the skin permeation of hydrophilic molecules.

Isolation and characterization of neurogenic mesenchymal stem cells in human scalp tissue.

Recent studies have shown that adult tissues contain stem/ progenitor cells capable of not only generating mature cells of their tissue of origin but also transdifferentiating themselves into other tissue cells. Murine skin-derived precursor cells, for example, have been described as unique, nonmesenchymal-like stem cells capable of mesodermal and ectodermal neurogenic differentiation. Human-derived skin precursors are less well characterized. In this study, the isolation and characterization of adherent, mesenchymal stem cell-like cells from human scalp tissue (hSCPs) are described. hSCPs initially isolated by both medium-selection (ms-hSCPs) and single-cell (c-hSCPs) methods were cultured in medium containing epidermal growth factor and fibroblast growth factor-beta. Cultured ms-hSCPs and c-hSCPs demonstrated a consistent growth rate, continuously replicated in cell culture, and displayed a stable phenotype indistinguishable from each other. Both hSCPs expressed surface antigen profile (CDw90, SH2, SH4, CD105, CD166, CD44, CD49d-e, and HLA class I) similar to that of bone marrow mesenchymal stem cells (BM-MSCs). The growth kinetics, surface epitopes, and differentiation potential of c-hSCP cells were characterized and compared with BM-MSCs. In addition to differentiation along the osteogenic, chondrogenic, and adipogenic lineages, hSCPs can effectively differentiate into neuronal precursors evident by neurogenic gene expression of glial fibrillary acid protein, NCAM, neuron filament-M, and microtubule-associated protein 2 transcripts. Therefore, hSCPs may potentially be a better alternative of BM-MSCs for neural repairing, in addition to their other mesenchymal regenerative capacity. Our study suggests that hSCPs may provide an alternative adult stem cell resource that may be useful for regenerative tissue repair and autotransplantations.

Syringocystadenocarcinoma papilliferum: successfully treated with Mohs micrographic surgery.

BACKGROUND: Syringocystadenocarcinoma papilliferum, a rare sweat gland carcinoma, is the malignant counterpart of syringocystadenoma papilliferum. OBJECTIVE: To demonstrate a rare case of syringocystadenocarcinoma papilliferum successfully treated with Mohs micrographic surgery. METHODS: A 60-year-old male presented with two verrucous plaques on his right auricle since childhood. These two plaques became ulcerated, more painful, and pruritic in 1 year. Histopathologic examination revealed syringocystadenocarcinoma papilliferum. RESULTS: Mohs micrographic surgery with reconstruction of right auricle was performed subsequently. There are no signs of recurrence or metastasis 6 years after operation. CONCLUSION: Syringocystadenocarcinoma papilliferum can be successfully treated with Mohs micrographic surgery.

The distribution of follicular units in the Chinese scalp: implications for reconstruction of natural-appearing hairlines in Orientals.

BACKGROUND: Follicular transplantation using hair in its naturally occurring groups, called follicular units (FUs), has become the most popular technique in hair restoration surgery. Recently follicular transplantation was performed with a qualitative and quantitative concept to achieve the best clinical result. The characteristics and distribution of FUs are well studied in Caucasians and widely applied in hair transplantation surgery. OBJECTIVE: In order to understand the normal distribution of FUs in the Chinese scalp, we counted the number of hairs and FUs in normal Chinese scalp to provide general information for surgical planning and design in bald Chinese patients. METHODS: A total of 50 normal and 50 bald Chinese adults were enrolled to count the hairs on their scalp. One hundred bald patients receiving hairline reconstruction were also prospectively quantitatively evaluated. RESULTS: In normal Chinese scalp, an average 71.78 FUs/cm(2) and 137.08 hairs/cm(2) were calculated with a follicular density of 1.91 hairs/FU. Two-hair FUs are the predominate group (50.29%). In bald patients, an average of 68.07 FUs/cm(2) was found, which was less than that of the occipital scalp in normal nonbald patients. In reconstruction of the frontal hairline, a total of 700-1000 FUs were implanted with an average density of 30 FUs/cm(2). CONCLUSION: We found the average number of FUs (0.72 FU/mm(2)) was less than that in Caucasian patients (1 FU/mm(2)). The average density of 30 FUs/cm(2) implanted was suitable to reconstruct a natural frontal hairline in bald Chinese patients, which can achieve about 40% of normal hair density. Our results could provide the hair surgeon with general information about hair distribution on the Chinese scalp for surgical planning and design in their patients.