The microfollicle: a model of the human hair follicle for in vitro studies.

Access to complex in vitro models that recapitulate the unique markers and cell-cell interactions of the hair follicle is rather limited. Creation of scalable, affordable, and relevant in vitro systems which can provide predictive screens of cosmetic ingredients and therapeutic actives for hair health would be highly valued. In this study, we explore the features of the microfollicle, a human hair follicle organoid model based on the spatio-temporally defined co-culture of primary cells. The microfollicle provides a 3D differentiation platform for outer root sheath keratinocytes, dermal papilla fibroblasts, and melanocytes, via epidermal-mesenchymal-neuroectodermal cross-talk. For assay applications, microfollicle cultures were adapted to 96-well plates suitable for medium-throughput testing up to 21 days, and characterized for their spatial and lineage markers. The microfollicles showed hair-specific keratin expression in both early and late stages of cultivation. The gene expression profile of microfollicles was also compared with human clinical biopsy samples in response to the benchmark hair-growth compound, minoxidil. The gene expression changes in microfollicles showed up to 75% overlap with the corresponding gene expression signature observed in the clinical study. Based on our results, the cultivation of the microfollicle appears to be a practical tool for generating testable insights for hair follicle development and offers a complex model for pre-clinical substance testing.

Alterations in Hair Follicle Morphology and Hair Shaft Production After Follicular Unit Transplantation.

Follicular unit transplantation is the most commonly performed technique in modern restorative hair transplantation surgery. It relies on the acquisition of intact follicular units from microdissected scalp skin strips and their subsequent transplantation into the recipient regions affected by alopecia. Ideally, the translocation of follicular units from the balding-resistant areas of the scalp (usually the occipital region) to the recipient site should not result in any morphological change in the grafts. Nevertheless, the insults associated with surgical intervention present grafted follicles to mechanical and chemical cues differently from those of the physiological steady-state conditions in undamaged skin. This disruption of the normal follicular microenvironment might alter important aspects of hair biology in grafts, for example, hair cycle and pigmentation, and, in turn, could lead to differences in hair appearance, eventually culminating in a diminished esthetical outcome of the surgery. In this study, the authors analyzed native and grafted scalp hair follicles (HFs) from 2 patients who had undergone follicular unit transplantation surgeries formerly. Scanning electron microscopy and light microscopy-based histomorphometry revealed a marked enlargement of follicular structures in the grafts with a concomitant increase in hair shaft diameter. Immunohistological staining confirmed a thickening of the dermal sheath in transplanted HFs that also harbored a denser vascular network. Taken together, these results show that the grafted HFs analyzed were subjected to marked morphological changes during their residence in the recipient site and that this phenomenon is associated with a modulation of follicular vascularization.

Hair Follicle Plasticity with Complemented Immune-modulation Following Follicular Unit Extraction.

BACKGROUND: During hair transplantation as an effective therapy for androgenetic alopecia, hair follicles were typically trans-located from the nonaffected occipital to the balding frontal or vertex region of the scalp. Although this is an autologous intervention, the donor and recipient hair follicle tissue differ in composition and local environment. SETTINGS AND DESIGN: In two case studies, we investigated the changes in hair follicle morphology and the immune status of scalp and body hair follicles from different origins transplanted to the eyebrows and the frontal scalp using follicular unit extraction. RESULTS: Quantitative histomorphometry and immunohistochemistry revealed a transformation in hair follicle length and dermal papilla size of the scalp, chest and beard hair follicles, which had been re-extracted after a 6-month period posttransplantation. Furthermore, a significant infiltration of B and T lymphocytes as well as macrophages could be observed most prominently in the infundibulum of transplanted hair follicles. CONCLUSION: The presented results demonstrate that hair follicle units from different body sites are capable to replace miniaturized or degraded hair follicles in different recipient areas like scalp or eyebrows as they keep their intrinsic capability or acquire the potential to readjust plastically within the beneficiary skin region. The essential secretory crosstalk underlying the observed tissue remodeling is possibly mediated by the infiltrating immune cells.

Skin and hair on-a-chip: in vitro skin models versus ex vivo tissue maintenance with dynamic perfusion.

Substantial progress has been achieved over the last few decades in the development of skin equivalents to model the skin as an organ. However, their static culture still limits the emulation of essential physiological properties crucial for toxicity testing and compound screening. Here, we describe a dynamically perfused chip-based bioreactor platform capable of applying variable mechanical shear stress and extending culture periods. This leads to improvements of culture conditions for integrated in vitro skin models, ex vivo skin organ cultures and biopsies of single hair follicular units.