Mesenchymal stem cell therapy in skin: why and what for?

In recent years, few stem cells have gained as much clinical notoriety as mesenchymal stem cells. Indeed, MSCs are already in use for a range of systemic inflammatory and autoimmune conditions that also affect the skin, such as acute and chronic graft versus host disease or lupus erythematosus. Most interestingly, these cells are able to improve skin wound healing in multiple preclinical models and few patient series. An additional potential of these cells is the delivery of missing structural elements in skin inherited disorders. However, we here contend that MSCs are not appropriate for cell replacement therapies in the context of wound healing. Indeed, engraftment of cells in the dermis is poor in the absence of irradiation and the observed effects seem mainly due to paracrine factors. In this viewpoint, we favour the hypothesis of a replete niche and competition with resident mesenchymal populations in the dermis not allowing the engraftment of newly delivered MSCs. Consequently, we propose that the benefit of MSCs may be at least in part reproduced by the growth factors or immunomodulatory molecules that they produce. In any case, the rapid progress in this field has allowed the emergence of important questions in skin biology that need to be addressed in parallel with the predictable future use of MSCs in the clinic.     

Homocysteine may accelerate skin aging: a new chapter in the biology of skin senescence?

Skin aging has received tremendous attention in recent years by both scientists and the lay public. This article reviews the evidence that homocysteine, an intermediary sulfhydryl-containing amino acid implicated in atherosclerosis, can accelerate skin aging and the aging of internal organs (universal aging).     

Oral collagen supplementation for skin aging: A fad or the future?

In recent years, oral collagen supplements have become a popular and trendy treatment in the world of skin health. It has been widely marketed to consumers for purported benefits in wrinkle reduction, skin‐rejuvenation, skin‐aging reversal, and skin plumping. However, there are currently limited data available in the literature and much regarding its possible effects on the skin has yet to be fully elucidated and understood. Here, we summarize some of the prominent studies in the literature and offer an evaluation of oral collagen supplementation for skin health.     

Barrier creams – skin protectants: can you protect skin?

Barrier creams (BC) are used in hand care to protect the user against damage from surfactants and other irritants; their clinical value remains debatable; some reports indicate that inappropriate BC application might induce a deleterious rather than a beneficial effect. Since many cosmetic formulations contain 'skin protectants', we review concept, application, and efficacy from the pertinent scientific literature.     

Signalling and chemosensitivity assays in melanoma: is mutated status a prerequisite for targeted therapy?

Selection for targeted therapies in melanoma is currently based on the search for mutations in selected genes. We aimed at evaluating the interest of signalling and chemosensitivity studies in addition to genotyping for assessing the best suitable treatment in an individual patient. We extracted genomic DNA and melanoma cells from tumor tissue of a skin metastasis of a 17-year-old woman with stage IV melanoma progressing despite three successive lines of treatment. Despite the absence of mutation in BRAF, NRAS cKIT, the MAPK pathway was activated and a significant response to sorafenib, a mitogen-activated protein kinase (MAPK)/RAF inhibitor, was found in signalling and chemosensitivity assays. A treatment combining sorafenib and dacarbazine produced a partial response for 9 months, with marked necrosis in some lesions. Chemosensitivity assays and signalling pathway studies could be of great value in addition to genotyping for assessing the most appropriate treatment in melanoma.     

Environmental nickel pollution: does it protect against nickel allergy?

The Norwegian-Russian border area is polluted because of emissions from two local Russian nickel refineries. We patch tested the general adult population on both sides of the border. Only 7.2% of the Russian women were sensitized to nickel, compared with 27.5% of the Norwegian women. We suggest that long-term exposure to nickel may have induced immunologic tolerance in the Russian population.     

Paratumoral epidermal hyperplasia: a novel prognostic factor in thick primary melanoma of the skin?

There is a lack of histopathological factors to sub-stratify prognosis in pT3/4 melanoma primaries. In the presented pilot study, the prognostic significance of different clinical and histopathological parameters was studied in thick primary melanoma taking paratumoral epidermal hyperplasia (PTEH) into consideration. Of 1632 melanoma patients in the melanoma register of the Martin Luther University Halle-Wittenberg in the years 1980 to 1987, 16 cases with tumor thickness (TT) of the primary > or = 3 mm, documented metastasis-free follow-up of 10+ years after primary therapy and available histologic sections were compared with an adequate recurrence control group (n = 62) by PTEH and standard prognostic parameters. PTEH was demonstrable in 15 of 16 patients of the metastasis-free group (PTEH penetration depth 1.42 +/- 0.82 mm/mean +/- SD) and 27 of 62 of controls (0.29 +/- 0.46 mm), P < or = 0.001. Of the standard prognostic parameters, TT, sex, location, and lack of nevus association also correlated with metastasis. In multivariate analysis, PTEH > or = 1 mm was the single independent parameter with the highest (negative) association to recurrence (odds ratio 52.3). Occurrence of PTEH might predict a more moderate course of disease in thick melanoma. Thus, it might become an easily determinable and effective tool to sub-stratify prognosis in thick primary melanoma of the skin. Further studies are necessary to prove these findings.     

The skin microbiome and immune system: Potential target for chemoprevention?

There has been increasing interest in understanding the role of the human microbiome in skin diseases. Microbiome studies are being utilized in skin cancer research in numerous ways. Commensal bacteria are being studied as a potential tool to judge the biggest environmental risk of skin cancer, ultraviolet (UV) radiation. Owing to the recognized link of skin microbes in the process of inflammation, there have been theories linking commensal bacteria to skin cancer. Viral metagenomics has also provided insight into virus linked forms of skin cancers. Speculations can be drawn for skin microbiome that in a manner similar to gut microbiome, they can be involved in chemoprevention of skin cancer. Nonetheless, there are definitely huge gaps in our knowledge of the relationship of microbiome and skin cancers, especially in relation to chemoprevention. The utilization of microbiome in skin cancer research seems to be a promising field and may help yield novel skin cancer prevention and treatment options. This review focuses on recent utilization of the microbiome in skin cancer research, and it explores the potential of utilizing the microbiome in prevention, earlier diagnosis, and treatment of skin cancers.     

Polymorphic light eruption and skin cancer prevalence: is one protective against the other?

Background Ultraviolet (UV) radiation (UVR) interacts with chromophores in cutaneous cells with consequent antigenicity. The normal response to this is a downregulation of immune responsiveness. Failure of the immune system to downregulate and to ignore transient photoantigens in human skin results in polymorphic light eruption (PLE), the commonest of the photodermatoses. UVR initiates and promotes skin cancer (SC): UV‐induced immunosuppression permits the expansion of UV‐mutated clones of cells which ultimately lead to SC. Objectives Because there is increased immune surveillance and resistance to immune suppression following UVR exposure in PLE one might expect a protective effect of PLE against SC and, conversely, a reduced risk of PLE among patients with SC. Methods We therefore constructed a prospective case–control study to see if this were the case. Two groups were studied: a group comprising 214 patients with SC and 210 gender‐ and aged‐matched controls, and a group comprising 100 patients with PLE and 155 gender‐ and aged‐matched controls. Each participant answered a questionnaire aimed at establishing personal and family history of SC and photodermatoses. Skin type and exposure to UVR were also documented. Results The prevalence of PLE in people with SC was 7·5%, compared with 21·4% for controls (P < 0·001). The prevalence of SC in patients with PLE was 4% compared with 7·1% for controls. Conclusions Our results show (i) strong evidence of reduced PLE in patients with SC, and (ii) a trend for reduced SC in patients with PLE. The immunological basis of PLE may therefore confer protection against SC.     

Melanoma and nonmelanoma skin cancer chemoprevention: A role for nicotinamide?

Ultraviolet radiation (UVR) causes DNA damage in melanocytes by producing photolesions such as cyclobutane pyrimidine dimers and 8‐oxo‐7‐hydrodeoxyguanosine. The production of reactive oxygen species by UVR also induces inflammatory cytokines that, together with the inherent immunosuppressive properties of UVR, propagate carcinogenesis. Nicotinamide (Vitamin B₃) enhances DNA repair, modulates the inflammatory environment produced by UVR, and reduces UV‐induced immunosuppression. As nicotinamide reduces the incidence of actinic keratoses and nonmelanoma skin cancers in high‐risk individuals and enhances repair of DNA damage in melanocytes, it is a promising agent for the chemoprevention of melanoma in high‐risk populations.     

Microchimerism and skin disease: true-true unrelated?

Microchimerism, the stable presence of foreign cells in an individual, may result from trafficking during pregnancy or from organ or hematopoietic transplantation, and has been hypothesized to cause autoimmunity and certain skin diseases. Yet microchimeric cells are found in normal individuals and may be important to tissue repair. Thus microchimerism may be common, and finding microchimeric cells in diseased as well as normal tissue may be a "true-true unrelated" situation.