Cicatricial Alopecia Research Foundation meeting, May 2016: Progress towards the diagnosis, treatment and cure of primary cicatricial alopecias.

Primary cicatricial alopecias (PCAs) are a group of skin diseases in which there is progressive and permanent destruction of hair follicles followed by replacement with fibrous tissue. Unfortunately, by the time patients seek clinical evaluation of their hair loss, the skin is already inflamed and/or scarred, so there is little hope for a return to their normal hair growth pattern. Clinical and basic science investigations are now focusing on three forms of human PCA: lichen planopilaris (LPP), frontal fibrosing alopecia (FFA) and central centrifugal cicatricial alopecia (CCCA). Transcriptome, lipidome and other new technologies are providing new insight into the pathogenesis of some of these diseases that are being validated and further investigated using spontaneous and genetically engineered mouse models.

Overexpression of Hr links excessive induction of Wnt signaling to Marie Unna hereditary hypotrichosis.

Marie Unna hereditary hypotrichosis (MUHH) is a rare autosomal dominant hair disorder. Through the study of a mouse model, we identified a mutation in the 5'-untranslated region of the hairless (HR) gene in patients with MUHH in a Caucasian family. The corresponding mutation, named 'hairpoor', was found in mutant mice that were generated through N-ethyl-N-nitrosourea mutagenesis. Hairpoor mouse mutants display partial hair loss at an early age and progress to near alopecia, which resembles the MUHH phenotype. This mutation conferred overexpression of HR through translational derepression and, in turn, decreased the expression of Sfrp2, an inhibitor of the Wnt signaling pathway. This study indicates that the gain in function of HR also results in alopecia, as seen with the loss of function of HR, via abnormal upregulation of the Wnt signaling pathway.

The mesenchymal component of hair follicle neogenesis: background, methods and molecular characterization.

Hair follicle morphogenesis and regeneration occur by an extensive and collaborative crosstalk between epithelial and mesenchymal skin components. A series of pioneering studies, which revealed an indispensable role of follicular dermal papilla and dermal sheath cells in this crosstalk, has led workers in the field to study in detail the anatomical distribution, functional properties, and molecular signature of the trichogenic dermal cells. The purpose of this paper was to provide a practical summary of the development and recent advances in the study of trichogenic dermal cells. Following a short review of the relevant literature, the methods for isolating and culturing these cells are summarized. Next, the bioassays, both in vivo and in vitro, that enable the evaluation of trichogenic properties of tested dermal cells are described in detail. A list of trichogenic molecular markers identified by those assays is also provided. Finally, this methods review is completed by defining some of the major questions needing resolution.

Bioengineering the hair follicle: fringe benefits of stem cell technology.

Recent advances in epithelial stem cell biology have resulted in the isolation of hair follicle stem cells, which generate hair follicles when injected into immunodeficient mice. These isolated hair follicle epithelial stem cells must be combined with 'inductive' dermal cells to produce new hair follicles. The advent of techniques for cultivating inductive dermal cells and competent epithelial stem cells creates the opportunity to bioengineer hair follicles for the treatment of hair loss.

Lipids to the top of hair biology.

Little attention has been given to the impact of lipid metabolism on hair follicle biology and pathology. Three recent papers (one in the current issue) describe a major effect of altered lipid metabolism on hair growth. A direct link was made to at least one form of cicatricial alopecia, but the role lipids play in other follicular pathologies, such as the acneiform conditions, are inadequately explored and must be tested.

Anaplastic neoplasms arising from basal cellcarcinoma xenotransplants into SCID-beige mice.

BACKGROUND: An animal model for the study of basal cell carcinoma (BCC) is required to better understand its biology. Several attempts to grow BCC in immuno-incompetent animals have been only modestly successful. METHODS: To test the ability of BCC to grow in a mouse with complete and severe immuno-incompetence, 14 individual BCC were transplanted into the subcutaneous tissue of 18 SCID-beige mice (T, B and natural killer cell deficient). Light microscopy and immunophenotypic analyses were performed on primary BCC and first and seventh passage tumors. RESULTS: Transplantation of three BCC yielded rapidly growing anaplastic tumors for a tumor take of 18% (3/18). SCID-beige mice without tumor growth had mostly scars or epidermoid cysts at the transplant sites. The three patients whose BCC gave rise to the anaplastic tumors were significantly older than those without tumor growth (87 vs. 64, p = 0.001), but they did not differ with respect to BCC type or general health. These three anaplastic tumors were histologically and immunophenotypically similar, being composed of dyscohesive, pleomorphic cells that expressed vimentin and smooth muscle actin. In the first passage mice these tumors were locally invasive, tumor-forming nodules associated with an expansion of donor inflammatory cells (T and B lymphocytes and plasma cells), rare remnants of BCC epithelium and epidermoid cysts. By the seventh passage, the tumors were homogenous and metastasized widely throughout the mice. Changing transplantation location to the dermis to wound environment or supplementing the tumor with BCC-derived fibroblasts did not alter the phenotype or growth rate in SCID-beige mice. Anaplastic tumors also grew easily in SCID mice (T and B cell deficient). However, transplantation of the anaplastic tumors into normal mice (CB-17) or less severely immunodeficient mice (NCr and Balb/c: T and natural killer cell deficient) did not allow for growth. Furthermore, tumor growth could not be maintained in vitro. CONCLUSION: Empirically, these data suggest that BCC has the potential to become an aggressive metastatic neoplasm, given the right immune and stromal environment. Moreover, a functional B lymphocyte system appears to prevent this growth. As human lymphocytes also engraft in SCID-beige mice, the original host immune response could be responsible for the lack of tumor growth in the majority of xenografts. Furthermore, the anaplastic and metastatic phenotype of these BCC derived neoplasms may be the experimental equivalent of metastatic BCC and BCC associated with carcinosarcoma.