Effects of solar radiations on stratum corneum hydration: Part II, protective action of solar filters.

The skin surface lipids (SSLs) film, composed of sebum and keratinocyte membrane lipids, is crucial to the barrier function of the stratum corneum (SC). The first part of this study investigated the impact of solar radiation on the SC based on a novel hydration and dehydration approach using Raman spectroscopy. The SSLs were found to absorb solar light, and thus participate to the protection of the skin surface. However, the protective function of the SSLs may be limited and is dependent to the heterogenous distribution of SSLs over the body surface. To ensure comprehensive protection, synergistic measures such as the application of solar filters are necessary. In this second part of the study, we have evaluated the limits of the protection capacity of SSLs and explored the protective action of a solar filters on both SSLs composition and the water hydration and dehydration kinetics in the SC.

Ultraviolet B irradiation increases the expression of cornulin and retepin in human skin xenotransplants.

Cornulin (CRNN) and repetin (RPTN) belong to the fused-type S100 protein family. Although these proteins have been reported to be expressed in the granular layer of the epidermis and have been suggested to be associated with barrier formation in the epidermis, their exact function remains unclear. This study examined the effects of ultraviolet B (UVB) irradiation on CRNN and RPTN expression in human skin xenotransplantation. The CRNN expression increased in the granular layer of UVB-irradiated skin 2 days after UVB irradiation compared to that in sham-irradiated skin. Interestingly, CRNN signals were observed not only in the cytoplasm, but also in the peripheral regions of granular keratinocytes. In contrast, RPTN was rarely expressed in sham-irradiated skin; however, RPTN signals were markedly increased in the granular layer of the UVB-irradiated skin. In addition, activation of ERK1/2 and STAT3 was observed in UVB-irradiated skin. Accordingly, the present study demonstrated that CRNN and RPTN are novel proteins whose expression can be increased by UVB irradiation. The activation of ERK1/2 and STAT3 may be associated with the regeneration of a UVB-damaged epidermis, and CRNN and RPTN may be induced to repair any dysfunction in the epidermal barrier during this regeneration process.

Recommendations for using analytical anisotropic algorithm and AcurosXB for epidermal dose calculations in breast radiotherapy from an in vivo Gafchromic film study.

BACKGROUND AND PURPOSE: This study recommends clinical epidermal dose calculation methods based on in-vivo film measurements and registered skin dose distributions with the Eclipse (Varian Medical Systems) treatment planning system's Analytical Anisotropic Algorithm (AAA) and Acuros XB (AXB) dose calculation algorithms. MATERIALS AND METHODS: Eighteen AAA V13.6 breast plans were recalculated using AXB (dose to medium) V13.5 with the same beam parameters and monitor units as in the original plans. These are compared against in-vivo Gafchromic film measurements from the lateral and inferior breast regions. Three skin structures in the treatment planning system are evaluated: a surface layer of voxels of the body contour, a 0.2 cm internal skin rind, and a 0.5 cm internal skin rind. RESULTS: Systematic shifts are demonstrated between the film measurements of skin dose and the Eclipse dose calculations. On average, the dose to the surface layer of pixels is underestimated by AAA by 8% and overestimated by AXB by 3%. A 5 mm skin rind extended into the body can increase epidermal dose calculations on average by 8% for AAA and 4% for AXB. CONCLUSION: This is the first study to register in-vivo skin dose distributions in the breast to the treatment planning system for comparison. Based on the results from this study it is recommended that epidermal dose is calculated with a 0.5 cm skin rind for the AAA algorithm and with rind thickness up to 0.2 cm for the AXB algorithm.

Radiofrequency Treatment Attenuates Age-Related Changes in Dermal-Epidermal Junctions of Animal Skin.

The dermal-epidermal junction (DEJ) is essential for maintaining skin structural integrity and regulating cell survival and proliferation. Thus, DEJ rejuvenation is key for skin revitalization, particularly in age-related DEJ deterioration. Radiofrequency (RF) treatment, known for its ability to enhance collagen fiber production through thermal mechanisms and increase heat shock protein (HSP) expression, has emerged as a promising method for skin rejuvenation. Additionally, RF activates Piezo1, an ion channel implicated in macrophage polarization toward an M2 phenotype and enhanced TGF-ß production. This study investigated the impact of RF treatment on HSP47 and HSP90 expression, known stimulators of DEJ protein expression. Furthermore, using in vitro and aged animal skin models, we assessed whether RF-induced Piezo1 activation and the subsequent M2 polarization could counter age-related DEJ changes. The RF treatment of H2O2-induced senescent keratinocytes upregulated the expression of HSP47, HSP90, TGF-ß, and DEJ proteins, including collagen XVII. Similarly, the RF treatment of senescent macrophages increased Piezo1 and CD206 (M2 marker) expression. Conditioned media from RF-treated senescent macrophages enhanced the expression of TGF-ß and DEJ proteins, such as nidogen and collagen IV, in senescent fibroblasts. In aged animal skin, RF treatment increased the expression of HSP47, HSP90, Piezo1, markers associated with M2 polarization, IL-10, and TGF-ß. Additionally, RF treatment enhanced DEJ protein expression. Moreover, RF reduced lamina densa replication, disrupted lesions, promoted hemidesmosome formation, and increased epidermal thickness. Overall, RF treatment effectively enhanced DEJ protein expression and mitigated age-related DEJ structural changes by increasing HSP levels and activating Piezo1.

Exploring the Influence of Cold Plasma on Epidermal Melanogenesis In Situ and In Vitro.

Epidermal melanin synthesis determines an individual's skin color. In humans, melanin is formed by melanocytes within the epidermis. The process of melanin synthesis strongly depends on a range of cellular factors, including the fine-tuned interplay with reactive oxygen species (ROS). In this context, a role of cold atmospheric plasma (CAP) on melanin synthesis was proposed due to its tunable ROS generation. Herein, the argon-driven plasma jet kINPen® MED was employed, and its impact on melanin synthesis was evaluated by comparison with known stimulants such as the phosphodiesterase inhibitor IBMX and UV radiation. Different available model systems were employed, and the melanin content of both cultured human melanocytes (in vitro) and full-thickness human skin biopsies (in situ) were analyzed. A histochemical method detected melanin in skin tissue. Cellular melanin was measured by NIR autofluorescence using flow cytometry, and a highly sensitive HPLC-MS method was applied, which enabled the differentiation of eu- and pheomelanin by their degradation products. The melanin content in full-thickness human skin biopsies increased after repeated CAP exposure, while there were only minor effects in cultured melanocytes compared to UV radiation and IBMX treatment. Based on these findings, CAP does not appear to be a useful option for treating skin pigmentation disorders. On the other hand, the risk of hyperpigmentation as an adverse effect of CAP application for wound healing or other dermatological diseases seems to be neglectable.

Unraveling UVB effects: Catalase activity and molecular alterations in the stratum corneum.

AIM: Ultraviolet B (UVB) radiation can compromise the functionality of the skin barrier through various mechanisms. We hypothesize that UVB induce photochemical alterations in the components of the outermost layer of the skin, known as the stratum corneum (SC), and modulate its antioxidative defense mechanisms. Catalase is a well-known antioxidative enzyme found in the SC where it acts to scavenge reactive oxygen species. However, a detailed characterization of acute UVB exposure on the activity of native catalase in the SC is lacking. Moreover, the effects of UVB irradiation on the molecular dynamics and organization of the SC keratin and lipid components remain unclear. Thus, the aim of this work is to characterize consequences of UVB exposure on the structural and antioxidative properties of catalase, as well as on the molecular and global properties of the SC matrix surrounding the enzyme. EXPERIMENTS: The effect of UVB irradiation on the catalase function is investigated by chronoamperometry with a skin covered oxygen electrode, which probes the activity of native catalase in the SC matrix. Circular dichroism is used to explore changes of the catalase secondary structure, and gel electrophoresis is used to detect fragmentation of the enzyme following the UVB exposure. UVB induced alterations of the SC molecular dynamics and structural features of the SC barrier, as well as its water sorption behavior, are investigated by a complementary set of techniques, including natural abundance 13C polarization transfer solid-state NMR, wide-angle X-ray diffraction, Fourier transform infrared (FTIR) spectroscopy, and dynamic vapor sorption microbalance. FINDINGS: The findings show that UVB exposure impairs the antioxidative function of catalase by deactivating both native catalase in the SC matrix and lyophilized catalase. However, UVB radiation does not alter the secondary structure of the catalase nor induce any observable enzyme fragmentation, which otherwise could explain deactivation of its function. NMR measurements on SC samples show a subtle increase in the molecular mobility of the terminal segments of the SC lipids, accompanied by a decrease in the mobility of lipid chain trans-gauche conformers after high doses of UVB exposure. At the same time, the NMR data suggest increased rigidity of the polypeptide backbone of the keratin filaments, while the molecular mobility of amino acid residues in random coil domains of keratin remain unaffected by UVB irradiation. The FTIR data show a consistent decrease in absorbance associated with lipid bond vibrations, relative to the main protein bands. Collectively, the NMR and FTIR data suggest a small modification in the composition of fluid and solid phases of the SC lipid and protein components after UVB exposure, unrelated to the hydration capacity of the SC tissue. To conclude, UVB deactivation of catalase is anticipated to elevate oxidative stress of the SC, which, when coupled with subtle changes in the molecular characteristics of the SC, may compromise the overall skin health and elevate the likelihood of developing skin disorders.

KoCVAM-led development of phototoxicity alternative test method using reconstructed human epidermis model (KeraSkin™).

Phototoxicity is an acute toxic reaction induced by topical skin exposure to photoreactive chemicals followed by exposure to environmental light and thus chemicals that absorb UV are recommended to be evaluated for phototoxic potential. There are currently three internationally harmonized alternative test methods for phototoxicity. One of them is the in vitro Phototoxicity: RhE Phototoxicity test method (OECD TG498). Korean center for the Validation of Alternative Methods (KoCVAM) developed an in vitro phototoxicity test method using a KeraSkin™ reconstructed human epidermis model (KeraSkin™ Phototoxicity Assay) as a 'me-too' test method of OECD TG498. For the development and optimization of KeraSkin™ Phototoxicity Assay, the following test chemicals were used: 6 proficiency chemicals in OECD TG498 (3 phototoxic and 3 non-phototoxic), 6 reference chemicals in OECD Performance Standard No. 356 (excluding the proficiency test chemicals, 3 phototoxic and 3 non-phototoxic) and 13 additional chemicals (7 phototoxic and 6 non-phototoxic). Based on the test results generated from the test chemicals above, the overall predictive capacity of KeraSkin™ Phototoxicity Assay was calculated. In particular, the assay exhibited 100 % accuracy, 100 % sensitivity, and 100 % specificity. Therefore, it fulfills the requirements to be included as a 'me-too' test method in OECD TG498.

Efficacy of 233 nm LED far UV-C-radiation against clinically relevant bacterial strains in the phase 2/ step 2 in vitro test on basis of EN 14561 and on an epidermis cell model.

INTRODUCTION: Healthcare-acquired infections and overuse of antibiotics are a common problem. Rising emergence of antibiotic and antiseptic resistances requires new methods of microbial decontamination or decolonization as the use of far-UV-C radiation. METHODS: The microbicidal efficacy of UV-C radiation (222 nm, 233 nm, 254 nm) was determined in a quantitative carrier test and on 3D-epidermis models against Staphylococcus (S.) aureus, S.epidermidis, S.haemolyticus, S.lugdunensis, Klebsiella pneumoniae, and Pseudomonas aeruginosa. To mimic realistic conditions, sodium chloride solution, mucin, albumin, artificial saliva, artificial wound exudate and artificial sweat were used. RESULTS: In sodium chloride solution, irradiation with a dose of 40 mJ/cm2 (233 nm) was sufficient to achieve 5 lg reduction independent of bacteria genus or species. In artificial sweat, albumin and artificial wound exudate, a reduction >3 lg was reached for most of the bacteria. Mucin and artificial saliva decreased the reduction to <2 lg. On 3D epidermis models, reduction was lower than in the carrier test. CONCLUSION: UV-C radiation at 233 nm was proven to be efficient in bacteria inactivation independent of genus or species thus being a promising candidate for clinical use in the presence of humans and on skin/mucosa.

Vitiligo non-responding lesions to narrow band UVB have intriguing cellular and molecular abnormalities that may prevent epidermal repigmentation.

We have discovered that human vitiligo patients treated with narrow-band UVB (NBUVB) demonstrated localized resistance to repigmentation in skin sites characterized by distinct cellular and molecular pathways. Using immunostaining studies, discovery-stage RNA-Seq analysis, and confirmatory in situ hybridization, we analyzed paired biopsies collected from vitiligo lesions that did not repigment after 6 months of NBUVB treatment (non-responding) and compared them with repigmented (responding) lesions from the same patient. Non-responding lesions exhibited acanthotic epidermis, had low number of total, proliferative, and differentiated melanocyte (MC) populations, and increased number of senescent keratinocytes (KCs) and of cytotoxic CD8+ T cells as compared with responding lesions. The abnormal response in the non-responding lesions was driven by a dysregulated cAMP pathway and of upstream activator PDE4B, and of WNT/ß-catenin repigmentation pathway. Vitiligo-responding lesions expressed high levels of WNT10B ligand, a molecule that may prevent epidermal senescence induced by NBUVB, and that in cultured melanoblasts prevented the pro-melanogenic effect of α-MSH. Understanding the pathways that govern lack of NBUVB-induced vitiligo repigmentation has a great promise in guiding the development of new therapeutic strategies for vitiligo.

Alterations in epidermal function in type 2 diabetes: Implications for the management of this disease.

Epidermal function is regulated by numerous exogenous and endogenous factors, including age, psychological stress, certain skin disorders, ultraviolet irradiation and pollution, and epidermal function itself can regulate cutaneous and extracutaneous functions. The biophysical properties of the stratum corneum reflect the status of both epidermal function and systemic conditions. Type 2 diabetes in both murine models and humans displays alterations in epidermal functions, including reduced levels of stratum corneum hydration and increased epidermal permeability as well as delayed permeability barrier recovery, which can all provoke and exacerbate cutaneous inflammation. Because inflammation plays a pathogenic role in type 2 diabetes, a therapy that improves epidermal functions could be an alternative approach to mitigating type 2 diabetes and its associated cutaneous disorders.

Effect of ultraviolet C emitted from KrCl excimer lamp with or without bandpass filter to mouse epidermis.

It has been reported that 222-nm ultraviolet C (UVC) exerts a germicidal effect on bacteria and viruses as well as UV radiation emitted from a conventional germicidal lamp but is less toxic to the mammalian cells than that from a germicidal lamp. An excimer lamp filled with krypton chloride (KrCl) gas principally emits 222-nm UVC. However, the lamp also emits a wide band of wavelengths other than 222 nm, especially UVC at a longer wavelength than 222 nm and ultraviolet B, which cause DNA damage. There are some reports on the critical role of bandpass filters in reducing the harmful effect of UVC emitted from a KrCl excimer lamp in a human skin model and human subjects. However, the effectiveness of a bandpass filter has not been demonstrated in animal experiments. In the present study, mice were irradiated with UVC emitted from a KrCl excimer lamp with or without a bandpass filter. UVC emitted from an unfiltered KrCl lamp at doses of 50, 150 and 300 mJ/cm2 induced cyclobutyl pyrimidine dimer (CPD)-positive cells, whereas UVC emitted from a filtered lamp did not significantly increase CPD-positive cells in the epidermis. The present study suggested that the bandpass filter serves a critical role in reducing the harmful effect of emission outside of 222 nm to mouse keratinocytes.

Safety of 222 nm UVC Irradiation to the Surgical Site in a Rabbit Model.

For the prevention of surgical site infection (SSI), continuous disinfection could be helpful. Short wavelength ultraviolet radiation C (UVC) is highly bactericidal but shows cytotoxicity. Radiation of UVC with a wavelength of 222 nm to the skin is considered to be safe because it only reaches the stratum corneum. However, the safety of 222 nm irradiation to the surgical field not covered with skin is unknown. The purpose of this study was to examine the safety of 222 nm UVC irradiation on a surgical field in a rabbit model. Five types of tissue were surgically exposed and irradiated with 222 or 254 nm UVC. Immunohistological assessment against cyclobutane pyrimidine dimer (CPD), an index of DNA damage by UVC, was performed. The CPD-positive cell rate was significantly higher in the 254 nm group than in the other groups in all tissues. A 222 nm group showed significantly more CPD than control in fat tissue, but no significant difference in all other tissues. In fat tissue collected 24 h after irradiation, the 254 nm group showed higher CPD than the other groups, while the 222 nm group had reduced to the control level. These data suggest that 222 nm UVC irradiation could be a new method to safely prevent SSI.

The effects of UVB irradiance on aberrant epidermal proliferation: Novel insights on how to improve currently available sunscreens.

AIMS: Sunscreen use, which prolonged the time required to develop sunburn by reducing the irradiance (mW/cm2) of the UVB radiation, is thought to protect the skin from developing cancers. Recently, in addition to fluence (mJ/cm2), irradiance of the UVB radiation was demonstrated to play an important role leading to photocarcinogenesis of the skin. After equivalent fluence of UVB exposure, enhanced aberrant keratinocyte proliferation contributes significantly to the photocarcinogenic capacity of low irradiance (LI) UVB as compared to its high irradiance (HI) UVB counterpart. However, the mechanism involved remains unclear. MAIN METHODS: Relevant cell and animal models were employed to investigate the effects of equivalent UVB fluence administered at HI or LI on keratinocyte proliferation. Additionally, the mechanisms involved were also explored. KEY FINDINGS: We found that at equivalent fluence, LIUVB induces significantly higher reactive oxidative species (ROS) production, cell proliferation, as well as phosphorylated AKT (pAKT) expression in both cell and animal models as compare to its HIUVB counterpart. Pretreating cultured keratinocytes with antioxidant or AKT inhibitor significantly reduced the UVB-induced ROS, cell proliferation, and pAKT expression. Additionally, these pretreatments abrogate the difference between the LI and HIUVB treated keratinocytes. Similar findings were noted using animal model treated with AKT inhibitor. SIGNIFICANCE: In summary, at equivalent fluence, LIUVB induces significantly more aberrant epidermal proliferation via enhanced ROS and pAKT signaling. Reducing UVB-induced AKT phosphorylation presents a novel strategy to improve the protective capacity of the currently available sunscreens.

Transcriptomic analysis of human skin wound healing and rejuvenation following ablative fractional laser treatment.

Ablative fractional laser treatment is considered the gold standard for skin rejuvenation. In order to understand how fractional laser works to rejuvenate skin, we performed microarray profiling on skin biopsies to identify temporal and dose-response changes in gene expression following fractional laser treatment. The backs of 14 women were treated with ablative fractional laser (Fraxel®) and 4 mm punch biopsies were collected from an untreated site and at the treated sites 1, 3, 7, 14, 21 and 28 days after the single treatment. In addition, in order to understand the effect that multiple fractional laser treatments have on skin rejuvenation, several sites were treated sequentially with either 1, 2, 3, or 4 treatments (with 28 days between treatments) followed by the collection of 4 mm punch biopsies. RNA was extracted from the biopsies, analyzed using Affymetrix U219 chips and gene expression was compared between untreated and treated sites. We observed dramatic changes in gene expression as early as 1 day after fractional laser treatment with changes remaining elevated even after 1 month. Analysis of individual genes demonstrated significant and time related changes in inflammatory, epidermal, and dermal genes, with dermal genes linked to extracellular matrix formation changing at later time points following fractional laser treatment. When comparing the age-related changes in skin gene expression to those induced by fractional laser, it was observed that fractional laser treatment reverses many of the changes in the aging gene expression. Finally, multiple fractional laser treatments, which cover different regions of a treatment area, resulted in a sustained or increased dermal remodeling response, with many genes either differentially regulated or continuously upregulated, supporting previous observations that maximal skin rejuvenation requires multiple fractional laser treatments. In conclusion, fractional laser treatment of human skin activates a number of biological processes involved in wound healing and tissue regeneration.

Stem cell spreading dynamics intrinsically differentiate acral melanomas from nevi.

Early differential diagnosis between malignant and benign tumors and their underlying intrinsic differences are the most critical issues for life-threatening cancers. To study whether human acral melanomas, deadly cancers that occur on non-hair-bearing skin, have distinct origins that underlie their invasive capability, we develop fate-tracing technologies of melanocyte stem cells in sweat glands (glandular McSCs) and in melanoma models in mice and compare the cellular dynamics with human melanoma. Herein, we report that glandular McSCs self-renew to expand their migratory progeny in response to genotoxic stress and trauma to generate invasive melanomas in mice that mimic human acral melanomas. The analysis of melanocytic lesions in human volar skin reveals that genetically unstable McSCs expand in sweat glands and in the surrounding epidermis in melanomas but not in nevi. The detection of such cell spreading dynamics provides an innovative method for an early differential diagnosis of acral melanomas from nevi.

Time kinetics of cyclobutane pyrimidine dimer formation by narrowband and broadband UVB irradiation.

BACKGROUND: Maximum cyclobutane pyrimidine dimer (CPD) formation in the skin induced by ultraviolet B (UVB) irradiation is thought to occur within a few minutes and is immediately decreased by the DNA repair system. OBJECTIVE: We evaluated the time course and differential effects of narrowband (NB-UVB) and broadband (BB-UVB) UVB on CPD formation. METHODS: We investigated CPD formation at various time-points in vivo, from 3 min to 72 h, after UVB irradiation using 2 mouse strains, C57BL/6 J and BALB/c. The backs of the mice were shaved and irradiated with NB-UVB or BB-UVB. Skin specimens were obtained and stained with anti-CPD antibody. Positive signals in the epidermis were measured using ImageJ. DNA was extracted from the isolated epidermis and subjected to quantitative CPD analysis by enzyme-linked immunosorbent assay (ELISA). RESULTS: CPDs induced by UVB irradiation (1 minimum erythemal dose) in epidermal skin were detected in the nucleus. Although the CPD levels increased immediately after irradiation (3 min), the highest level was detected at 1 h and the increase lasted 24-48 h after irradiation. BB-UVB tended to induce greater CPD levels than NB-UVB in both mouse strains. The ELISA showed similar results. CONCLUSIONS: CPDs were induced immediately after UV irradiation, with the maximum level observed 1 h after irradiation. BB-UVB irradiation tended to induce greater levels of CPD formation. In addition to the direct effects of UVB, the presence of CPDs in hair follicles, which were not irradiated by UVB, suggests that reactive oxygen species are also involved in CPD formation in the skin.

Protective effect of taurine on UVB-induced skin aging in hairless mice.

Taurine, a sulfur-containing amino acid derivative, exists at a high concentration in the skin and is considered to play an important role in maintaining moisture homeostasis. This study investigated the effects of oral taurine supplementation on epidermal moisture content and wrinkle formation, as well as skin taurine content, using ultraviolet B (UVB)-irradiated hairless mice. Wrinkles were induced by exposing hairless mice to UVB radiation (70-100 mJ/cm2). Taurine was dissolved in drinking water at a concentration of 0.3 or 3% (w/v) and given to the mice ad libitum for 2-10 weeks. Taurine was then extracted from the dorsal skin, and the skin taurine content was determined using high-performance liquid chromatography (HPLC). The wrinkles were evaluated using a wrinkle score and the quantitative wrinkle area ratio. The exposure of the mice to UVB radiation for 4 weeks resulted in a decreased moisture content and increased transepidermal water loss (TEWL) in the skin, while taurine supplementation suppressed these changes. Oral supplementation with taurine for 8 weeks ameliorated the development of UVB-induced wrinkle formation. Furthermore, oral taurine supplementation for 4 weeks decreased pre-stablished wrinkles in a dose-dependent manner. Although the UVB radiation reduced the epidermal taurine content, oral taurine supplementation partly restored the taurine content in the epidermis. The present study showed that oral taurine supplementation is able to suppress UVB-induced wrinkle formation, which may be associated with the regulation of moisture content in the epidermis. The beneficial effects of taurine on skin aging may be attributed to its osmoregulatory role.

The regional distribution of melanosomes in the epidermis affords a localized intensive photoprotection for basal keratinocyte stem cells.

Human skin is a highly efficient self-renewing barrier that is critical to withstanding environmental insults. Undifferentiated keratinocyte stem cells reside in the basal layer of the epidermis and in hair follicles that continuously give rise to progenies ensuring epidermal turnover and renewal. Ultraviolet (UV) radiation is a proven cause of skin keratinocyte cancers, which preferentially occur at sun-exposed areas of the skin. Fortunately, melanocytes produce melanin that is packaged in specific organelles (termed melanosomes) that are then delivered to nearby keratinocytes, endowing the recipient cells with photoprotection. It has long been thought that melanosome transfer takes place stochastically from melanocytes to keratinocytes via an as-yet-unrecognized manner. However, recent studies have indicated that melanosomes are distributed regionally in the basal layer of the skin, affording localized intensive photoprotection for progenitor keratinocytes and stem cells that reside in the microenvironment of the basal epidermis. In this review, we summarize current knowledge about molecular and cellular mechanisms that are responsible for the selective transfer and exclusive degradation of melanosomes in the epidermis, emphasizing implications for skin carcinogenesis.

Microneedle based adipose derived stem cells-derived extracellular vesicles therapy ameliorates UV-induced photoaging in SKH-1 mice.

Extracellular vesicles from adipose derived stem cells (ADSCs-EVs) have shown immunomodulation and anti-photoaging effects; however, the skin barrier prevents their absorption via skin. Meanwhile, microneedle (MN) is a widely used and minimally invasive tool for dermal delivery of drugs, it also has neocollagenesis effect by creating tiny injuries and initiating wound healing process. To investigate the effect of MN combined with ADSCs-EVs on skin aging, photoaging in SKH-1 mice was induced by chronic exposure to ultraviolet radiation. Then the mice were treated following a split-dorsal scheme, in which one side had MN alone or MN + EVs treatment and the other side was left untreated. For the side treated with MN alone or MN + EVs, the epidermal thickness was decreased and the skin barrier function was enhanced compared with the untreated side. However, MN + EVs group showed the least wrinkles, the highest collagen density and the most organized collagen fibers among the three groups. The level of CD11b + cell infiltration was lower in MN + EVs group than that in the MN group at 3 day after the treatment. These results indicated that MN treatment alone could improve epidermal structure and function of photoaging skin, and a combination with ADSCs-EVs would accelerate the restoration of inflammation caused by MN and improve the content of collagen. In all, this study indicated that a combination of MN and topical applied ADSCs-EVs was a feasible and safe strategy to ameliorate photoaging, providing a new avenue for safe administration of EVs.