The physiological effects of chondroitin sulfate (CS) depend on the extent of its sulfation. This study focused on the effects of highly sulfated CS with different molecular weights in normal human dermal fibroblasts (NHDFs). NHDFs were treated with each CS. The expression of various genes was assessed by real-time PCR. Type I collagen content and elastin protein expression levels were assessed by ELISA and Western blotting, respectively. Disaccharide CS significantly increased the expression of genes required for extracellular matrix (collagen, type I, alpha I, decorin, elastin, lysyl oxidase, SMAD2 and SMAD3). In addition, we confirmed that collagen and elastin increased at the protein level. In contrast, high- and low-molecular-weight CS polymer had no significant effect. Therefore, highly sulfated disaccharide CS increased the expression of extracellular matrix-related genes and proteins. It may be possible that the highly sulfated disaccharide CS may increase firmness and elasticity of skin.

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Recently, various kinds of stem cells (ES cells, iPS cells, MUSE cells, mesenchymal stem cells in bone marrow, etc.) have been reported to be useful for regenerative medicine in neurological, ophthalmologic or cardiac disorders. However, ES cells are not allowed to use due to ethical matter in our country. In addition, MUSE cells, mesenchymal stem cells in bone marrow are hard to obtain and to multiply. Moreover, there hasn't been any method to induce epidermal keratinocytes from iPS cells. Therefore, in this study, we investigated whether keratinocyte progenitor cells are present in the adipose derived stem cells (ASCs) population. ASCs isolated from subcutaneous adipose tissue were cultured and examined for the expression of the keratinocyte progenitor markers p63 and desmoglein 3 (DSG3) by immunofluorescence microscopy and flow cytometry. In addition, p63 and DSG3 expression levels were assessed before and after differentiation of ASCs into adipocytes by real-time PCR and western blot analysis, as well as in subcutaneous adipose tissue by real-time reverse transcriptase polymerase chain reaction. Both markers were expressed in ASCs, but were downregulated after the differentiation of ASCs into adipocytes; p63-positive cells were also detected in subcutaneous adipose tissue. ASCs co-cultured with human fibroblasts and incubated with all-trans retinoic acid and bone morphologic protein 4 showed an upregulation in DSG3 level, which was also increased in the presence of type IV collagen. They also showed an upregulation in cytokeratin-5 level only in the presence of type IV collagen. These results provide the demonstration that keratinocyte progenitor cells reside in subcutaneous adipose tissue.

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The cosmetics may be used by vast numbers of individuals, extensively over a large part of their lifespan. Therefore, great care should be taken with them and well designed investigations should be conducted to obtain greater guarantees so that they can be used safely. It is essential that attention be paid to potential toxicological hazards to consumers at an early stage when developing new products. Safety can be defined as freedom from danger or risk, but absolute safety does not exist. The concept of risk/benefit balance has been developed. As there is no way to guarantee total absence of risk, some kind of pragmatic approach to reaching decisions on risk acceptability is certainly needed for cosmetics. This risk/benefit balance varies with the categories of products. The “non-essential” products like cosmetics must not give rise to any risk. “To what extent we should assure the safety of cosmetics” when we actually make the assessment of them. We should guarantee the safety-in-use of the products. The practical safety assessment process starts with the review of the existing information. The actual safety assessment procedures for ingredients and finished products will vary according to the product and its intended use. Then we determine from all of this information, what we need to focus on or what may be a question or problem to be solved. It must be stressed that there is no textbook formula procedure which can be followed and that the sequence can vary considerably with different ingredients and products. However, adequate series of toxicity studies should be performed especially with newly developed components in order to enable reliable conclusions to be made on potential harmful effects. The post-marketing safety re-evaluation may be necessary. Toxicological and safety evaluation techniques are ever-advancing. Questions may arise about the safety of products, on the market for a long time and previously regarded as safe, as a reflection of new scientific developments. The investigators in charge of the safety assessment should be very sensitive to the related information with wide knowledge and experiment, to make the above-mentioned pre- and post-marketing assessment more precise.

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There are various types of side effects caused by cosmetics; mostly they are believed to be not serious. Further, there are not a few cases at present that it is difficult to identify which ingredients in cosmetic products caused; even it was certainly caused by cosmetics which had been used. It herewith refers the actual cases which were implemented some measures by MHLW (Ministry of Health, Labour and Welfare of Japan) under the jurisdiction of Pharmaceutical Affairs Law or JCIA (Japan Cosmetic Industry Association) as a representative of cosmetic industries, taking into account the cases must be caused by cosmetics (including quasi-drugs such as medicated cosmetics). It also covers the background and history of cosmetic regulation under the Pharmaceutical Affairs Law in considering the safety of cosmetics.

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Lawsuits related to perfumery and cosmetics are increasing recently in Japan. Especially, products liability (PL) suits are important. Among the PL lawsuits, wheat induced anaphylaxy due to hydrolyzed wheat as ingredients, Gefitinib lawsuits and rhododenol induced vitiligo are suspected to the smash effects on the number of PL suits in Japan. However, compared to PL suits in USA, the number and jurisdictional amount in USA are much larger than those of Japan. Some judgement cases on perfumery and cosmetics PL suits and mal-usage cases in beauty salons are reported briefly in this article.

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