Sequential Scalp Assessment in Hair Regeneration Therapy Using an Adipose-Derived Stem Cell-Conditioned Medium.

BACKGROUND: An adipose-derived stem cell-conditioned medium (ADSC-CM) reportedly exerts skin-rejuvenating and hair growth-promoting effects. In the therapeutic application of ADSC-CM for alopecia, changes to the interfollicular scalp remain unclear although some evidence has indicated hair growth-promoting effects. OBJECTIVE: To evaluate the effects of ADSC-CM not only on hair follicles, but also on the interfollicular scalp. METHODS: Forty patients (21 men, 19 women; age range, 23-74 years) with alopecia were treated by intradermal injection of ADSC-CM every month for 6 months. Eighty fixed sites on patients were investigated by trichograms, physiological examinations, and ultrasonographic examinations at 4 time points (before treatment and 2, 4, and 6 months after the initial treatment). RESULTS: Hair density and anagen hair rate increased significantly. As physiological parameters, transepidermal water loss value gradually increased, with significant differences at 4 and 6 months after the initial treatment, but hydration state of the stratum corneum and skin surface lipid level showed no obvious changes. As ultrasonographic parameters, dermal thickness and dermal echogenicity were increased significantly. CONCLUSION: Intradermal administration of ADSC-CM on the scalp has strong potential to provide regenerative effects for hair follicles and the interfollicular scalp. An adipose-derived stem cell-conditioned medium offers a promising prospect as an alternative treatment for alopecia.

Carcinogenicity assessment of the Hedgehog pathway inhibitor, vismodegib in Tg.rasH2 mice and Sprague-Dawley rats.

Vismodegib (also known as GDC-0449) is a novel small molecule inhibitor of the Hedgehog (Hh) signaling pathway currently approved for the treatment of metastatic or locally advanced basal cell carcinoma (BCC) in humans. Its tumorigenic potential was assessed in dedicated carcinogenicity studies in rasH2 transgenic (Tg.rasH2) mice and Sprague Dawley (SD) rats. Tumorigenicity potential of vismodegib was identified in rats only and was limited to benign hair follicle tumors, including pilomatricomas and keratoacanthomas at exposures of ≥0.1-fold and ≥0.6-fold, respectively, of the steady-state exposure (AUC0-24h) of the recommended human dose. No malignant tumors were identified in either species. Overall, the totality of pharmacology and nonclinical safety data (lack of genotoxicity, in vitro secondary pharmacological binding, and immunoregulatory effects, and limited effects on the endocrine system) suggests that the development of the benign hair follicle tumors may be related to pharmacologically-mediated disruption of hair follicle morphogenesis, although the exact mechanism of tumorigenesis is unclear. Hair follicle tumors have not been reported in vismodegib-treated patients. The relevance of this finding in rats to patients is uncertain.

Histological assessment of follicular delivery of flutamide by solid lipid nanoparticles: potential tool for the treatment of androgenic alopecia.

CONTEXT: Flutamide is a potent anti-androgen with the several unwanted side effects in systemic administration, therefore, it has attracted special interest in the development of topically applied formulations for the treatment of androgenic alopecia. OBJECTIVE: The purpose of this study was to prepare and characterize the solid lipid nanoparticles (SLNs) of Flutamide for follicular targeting in the treatment of the androgenic alopecia. METHODS: Flutamide-loaded SLNs, promising drug carriers for topical application were prepared by hot melt homogenization method. Drug permeation and accumulation in the exercised rat skin and histological study on the male hamsters were performed to assess drug delivery efficiency in vitro and in vivo, respectively. RESULTS: The optimized Flutamide-loaded SLNs (size 198 nm, encapsulation efficiency percentage 65% and loading efficiency percentage 3.27%) exhibited a good stability during the period of at least 2 months. The results of X-ray diffraction showed Flutamide amorphous state confirming uniform drug dispersion in the SLNs structure. Higher skin drug deposition (1.75 times) of SLN formulation compared to Flutamide hydroalcoholic solution represented better localization of the drug in the skin. The in vivo studies showed more new hair follicle growth by utilizing Flutamide-loaded SLNs than Flutamide hydroalcoholic solution which could be due to the higher accumulation of SLNs in the hair follicles as well as slowly and continues release of the Flutamide through the SLNs maximizing hair follicle exposure by antiandrogenic drug. CONCLUSION: It was concluded Flutamide-loaded SLN formulation can be used as a promising colloidal drug carriers for topical administration of Flutamide in the treatment of androgenic alopecia.

Retinoic acid and dimethyl sulfoxide promote efficient delivery of transgenes to mouse skin by topically transdermal penetration.

Simple and efficient gene transfer to the skin would facilitate many local and systemic gene therapy applications. This study reports a novel approach that allows expression of plasmid DNA in epidermis and hair follicle cells with dimethyl sulfoxide (DMSO) after pre-treatment with depilation and retinoic acid (RA) for the purposes of gene therapy. This study investigated the transdermal efficacy of gene to mouse skin when utilizing DMSO after RA pre-treatment. Retinoic acid pre-treatment can increase the efficiency of transfection. This finding indicates that one can more effectively and much less expensively make use of genes therapy to treat diseases of the hair and skin.