Pharmacological and Genetic Inhibition of Caveolin-1 Promotes Epithelialization and Wound Closure.

Chronic wounds-including diabetic foot ulcers, venous leg ulcers, and pressure ulcers-represent a major health problem that demands an urgent solution and new therapies. Despite major burden to patients, health care professionals, and health care systems worldwide, there are no efficacious therapies approved for treatment of chronic wounds. One of the major obstacles in achieving wound closure in patients is the lack of epithelial migration. Here, we used multiple pre-clinical wound models to show that Caveolin-1 (Cav1) impedes healing and that targeting Cav1 accelerates wound closure. We found that Cav1 expression is significantly upregulated in wound edge biopsies of patients with non-healing wounds, confirming its healing-inhibitory role. Conversely, Cav1 was absent from the migrating epithelium and is downregulated in acutely healing wounds. Specifically, Cav1 interacted with membranous glucocorticoid receptor (mbGR) and epidermal growth factor receptor (EGFR) in a glucocorticoid-dependent manner to inhibit cutaneous healing. However, pharmacological disruption of caveolae by MßCD or CRISPR/Cas9-mediated Cav1 knockdown resulted in disruption of Cav1-mbGR and Cav1-EGFR complexes and promoted epithelialization and wound healing. Our data reveal a novel mechanism of inhibition of epithelialization and wound closure, providing a rationale for pharmacological targeting of Cav1 as potential therapy for patients with non-healing chronic wounds.

Effectiveness of Platelet-Rich Plasma for Androgenetic Alopecia: A Review of the Literature.

Androgenetic alopecia (AGA) is a hair loss disorder affecting 80% of men and 50% of women throughout their lifetime. Therapies for AGA are limited and there is no cure. There is a high demand for hair restoration. Platelet-rich plasma (PRP), a treatment modality shown to promote wound healing, has also been explored as a treatment for AGA. This literature review was conducted to assess the effectiveness of PRP treatment for AGA. Twelve studies conducted from 2011 to 2017 were evaluated and summarized by study characteristics, mode of preparation, and treatment protocols. A total of 295 subjects were given PRP or control treatment in these studies, and evaluated for terminal hair density, hair quality, anagen/telogen hair ratio, keratinocyte proliferation, blood vessel density, etc. Some studies also provided subject self-assessment reports. Most of the studies reviewed showed effectiveness of PRP in increasing terminal hair density/diameter. Additional investigations are needed to determine the optimal treatment regimen for high efficacy of PRP in AGA.

Low-level laser therapy for the treatment of androgenic alopecia: a review.

There are many new low-level laser technologies that have been released commercially that claim to support hair regrowth. In this paper, we will examine the clinical trials to determine whether the body of evidence supports the use of low-level laser therapy (LLLT) to treat androgenic alopecia (AGA). A literature search was conducted through Pubmed, Embase, and Clinicaltrials.gov for clinical trials using LLLT to treat AGA. Thirteen clinical trials were assessed. Review articles were not included. Ten of 11 trials demonstrated significant improvement of androgenic alopecia in comparison to baseline or controls when treated with LLLT. In the remaining study, improvement in hair counts and hair diameter was recorded, but did not reach statistical significance. Two trials did not include statistical analysis, but showed marked improvement by hair count or by photographic evidence. Two trials showed efficacy for LLLT in combination with topical minoxidil. One trial showed efficacy when accompanying finasteride treatment. LLLT appears to be a safe, alternative treatment for patients with androgenic alopecia. Clinical trials have indicated efficacy for androgenic alopecia in both men and women. It may be used independently or as an adjuvant of minoxidil or finasteride. More research needs to be undertaken to determine the optimal power and wavelength to use in LLLT as well as LLLT's mechanism of action.

A review of monochromatic light devices for the treatment of alopecia areata.

There are many laser technologies that are being tested that claim to support hair regrowth for patients with alopecia areata (AA). In this paper, we will determine whether the body of evidence supports the use of devices using monochromatic light sources to treat AA. Articles were gathered from PubMed, Embase, and the Cochrane database using these keywords: lasers, excimer laser, low-level laser therapy (LLLT), low-level light therapy, alopecia, alopecia areata, and hair loss with a category modifier of English. Ten clinical trials and seven case reports/abstracts were assessed. Eight clinical trials and two case reports demonstrated hair regrowth with the 308-nm excimer laser/light in men, women, and children. One case report demonstrated hair regrowth with the ALBA 355® laser. One clinical trial and two case reports demonstrated hair regrowth with LLLT. While two case reports demonstrated hair regrowth with fractional laser therapy, one clinical trial showed no improvement. The 308-nm excimer laser is a safe and effective treatment for men, women, and children with refractory AA of the scalp and beard. Larger, double-blinded clinical trials should be conducted to compare excimer laser therapy to standard treatments. More data is needed to determine the efficacy of LLLT and fractional laser therapy in the treatment of AA.

Epidermal Differentiation in Barrier Maintenance and Wound Healing.

Significance: The epidermal barrier prevents water loss and serves as the body's first line of defense against toxins, chemicals, and infectious microbes. Disruption of the barrier, either through congenital disorders of barrier formation or through wounds, puts the individual at risk for dehydration, hypersensitivity, infection, and prolonged inflammation. Epidermal barrier disorders affect millions of patients in the United States, causing loss of productivity and diminished quality of life for patients and their families, and represent a burden to the health-care system and society. Recent Advances: The genetic basis of many congenital barrier disorders has been identified in recent years, and great advances have been made in the molecular mechanisms of the formation and homeostasis of epidermal barrier, as well as acute and chronic wound healing. Progress in stem cell (SC) biology, particularly in induced pluripotent stem cells (iPSCs) and allogeneic mesenchymal stem cells (MSCs), has opened new doors for cell-based therapy of chronic wounds. Critical Issues: Understanding of the molecular mechanisms of barrier homeostasis in health and disease, as well as contributions of iPSCs and allogeneic MSCs to wound healing, will lead to the identification of novel targets for developing therapeutics for congenital barrier and wound healing disorders. Future Directions: Future studies should focus on better understanding of molecular mechanisms leading to disrupted homeostasis of epidermal barrier to identify potential therapeutic targets to combat its associated diseases.

Low-level laser treatment accelerated hair regrowth in a rat model of chemotherapy-induced alopecia (CIA).

Chemotherapy-induced alopecia (CIA) is one of the most distressing side effects of antineoplastic chemotherapy for which there is no effective interventional approach. A low-level laser (LLL) device, the HairMax LaserComb®, has been cleared by the FDA to treat androgenetic alopecia. Its effects may be extended to other settings; we have demonstrated that LaserComb treatment induced hair regrowth in a mouse model for alopecia areata. In the current study, we tested whether LLL treatment could promote hair regrowth in a rat model for CIA. Chemotherapy agents cyclophosphamide, etoposide, or a combination of cyclophosphamide and doxorubicin were administered in young rats to induce alopecia, with or without LLL treatment. As expected, 7-10 days later, all the rats developed full body alopecia. However, rats receiving laser treatment regrew hair 5 days earlier than rats receiving chemotherapy alone or sham laser treatment (with the laser turned off). The accelerated hair regrowth in laser-treated rats was confirmed by histology. In addition, LLL treatment did not provide local protection to subcutaneously injected Shay chloroleukemic cells. Taken together, our results demonstrated that LLL treatment significantly accelerated hair regrowth after CIA without compromising the efficacy of chemotherapy in our rat model. Our results suggest that LLL should be explored for the treatment of CIA in clinical trials because LLL devices for home use (such as the HairMax LaserComb®) provide a user-friendly and noninvasive approach that could be translated to increased patient compliance and improved efficacy.

Effects of the Lexington LaserComb on hair regrowth in the C3H/HeJ mouse model of alopecia areata.

Alopecia areata (AA) is a common autoimmune disease that presents with non-scarring alopecia. It is characterized by intra- or peri-follicular lymphocytic infiltrates composed of CD4+ and CD8+ T-cells on histology. To this day, few treatments are effective for AA. Here we present findings of using a low-level laser comb to alleviate the symptoms of AA in a C3H/HeJ mouse model for AA. Fourteen C3H/HeJ mice with induced AA were used in this study. Two were killed to confirm AA through histology. The remaining 12 mice were randomized into two groups; group I received HairMax LaserComb (wavelength: 655 nm, beam diameter <5 mm; divergence 57 mrad; nine lasers) for 20 s daily, three times per week for a total of 6 weeks; group II was treated similarly, except that the laser was turned off (sham-treated). After 6 weeks of LaserComb treatment, hair regrowth was observed in all the mice in group I (laser-treated) but none in group II (sham-treated). On histology, increased number of anagen hair follicles was observed in laser-treated mice. On the other hand, sham-treated mice demonstrated hair follicles in the telogen phase with no hair shaft. LaserComb seems to be an effective and convenient device for the treatment of AA in the C3H/HeJ mouse model. Human studies are required to determine the efficacy and safety of this device for AA therapy.

Prevention and treatment of alopecia areata with quercetin in the C3H/HeJ mouse model.

Alopecia areata (AA) is an autoimmune non-scarring hair loss disorder. AA can be acute, recurrent, or chronic. Current therapeutic options for AA are limited, and there is no effective prevention for recurrent AA. We have previously shown a correlation between the expression of HSP70 (HSPA1A/B), a heat shock protein involved in the inflammatory response, and the onset of AA in the C3H/HeJ mouse model. In this study, we tested the effects of quercetin, a bioflavonoid with anti-inflammatory properties, on AA development and HSP70 expression in the C3H/HeJ model. Mice with spontaneous AA were treated with subcutaneous quercetin or sham injections. Hair regrowth was observed in lesional areas in all the quercetin-treated mice, but in none of the sham-treated mice. In addition, non-alopecic C3H/HeJ mice were heat-treated to induce alopecia, along with quercetin or sham injections. Whereas 24% of the heat-treated mice with sham injections developed alopecia, none of the mice receiving quercetin injections did. As expected, the level of HSP70 expression in quercetin-treated areas was comparable to control. Furthermore, we showed that systemic delivery of quercetin by intraperitoneal injections prevented/reduced spontaneous onset of AA. Our results demonstrated that quercetin provided effective treatment for AA as well as prevention of onset of AA in the C3H/HeJ model, and warrant further clinical studies to determine whether quercetin may provide both treatment for preexisting AA and prevention of recurrent AA. The ready availability of quercetin as a dietary supplement may lead to increased patient compliance and positive outcomes for AA.

Cross-section Trichometry: A Clinical Tool for Assessing the Progression and Treatment Response of Alopecia.

BACKGROUND: To properly assess the progression and treatment response of alopecia, one must measure the changes in hair mass, which is influenced by both the density and diameter of hair. Unfortunately, a convenient device for hair mass evaluation had not been available to dermatologists until the recent introduction of the cross-section trichometer, which directly measures the cross-sectional area of an isolated bundle of hair. OBJECTIVE: We sought to evaluate the accuracy and sensitivity of the HairCheck(®) device, a commercial product derived from the original cross-section trichometer. MATERIALS AND METHODS: Bundles of surgical silk and human hair were used to evaluate the ability of the HairCheck(®) device to detect and measure small changes in the number and diameter of strands, and bundle weight. RESULTS: Strong correlations were observed between the bundle's cross-sectional area, displayed as the numeric Hair Mass Index (HMI), the number of strands, the silk/hair diameter, and the bundle dry weight. CONCLUSION: HMI strongly correlated with the number and diameter of silk/hair, and the weight of the bundle, suggesting that it can serve as a valid indicator of hair mass. We have given the name cross-section trichometry (CST) to the methodology of obtaining the HMI using the HairCheck(®) system. CST is a simple modality for the quantification of hair mass, and may be used as a convenient and useful tool to clinically assess changes in hair mass caused by thinning, shedding, breakage, or growth in males and females with progressive alopecia or those receiving alopecia treatment.

Heat treatment increases the incidence of alopecia areata in the C3H/HeJ mouse model.

Alopecia areata (AA) is a common autoimmune disease characterized by non-scarring hair loss. Previous studies have demonstrated an association between AA and physiological/psychological stress. In this study, we investigated the effects of heat treatment, a physiological stress, on AA development in C3H/HeJ mice. Whereas this strain of mice are predisposed to AA at low incidence by 18 months of age, we observed a significant increase in the incidence of hair loss in heat-treated 8-month-old C3H/HeJ mice compared with sham-treated mice. Histological analysis detected mononuclear cell infiltration in anagen hair follicles, a characteristic of AA, in heat-treated mouse skin. As expected, increased expression of induced HSPA1A/B (formerly called HSP70i) was detected in skin samples from heat-treated mice. Importantly, increased HSPA1A/B expression was also detected in skin samples from C3H/HeJ mice that developed AA spontaneously. Our results suggest that induction of HSPA1A/B may precipitate the development of AA in C3H/HeJ mice. For future studies, the C3H/HeJ mice with heat treatment may prove a useful model to investigate stress response in AA.