Adipose-derived stem cells (ADSCs) have been shown to induce wound-healing effects. Because inflammation near the wound area induces oxygen deficiency, it is interesting to elucidate the effect of hypoxia on the function of ADSCs. In this work, we asked: (1) does hypoxia alter the wound-healing function of ADSCs? and (2) what are the major factors responsible for the alteration in the wound-healing function? Effect of hypoxia on the proliferation of ADSCs was first examined that hypoxia (2% O(2)) enhanced the proliferation of ADSCs in either the presence of serum or in the absence of serum. The conditioned medium of ADSCs harvested under hypoxia (hypoCM) significantly promoted collagen synthesis and the migration of human dermal fibroblasts, compared with that in normoxia (norCM). In the animal studies, hypoCM significantly reduced the wound area compared with norCM. Furthermore, mRNA and protein measurements showed that hypoxia up-regulated growth factors such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). Inhibition of VEGF and bFGF using neutralizing antibodies reversed the migration of the wounded human dermal fibroblasts and the healing of wounds in animal experiment. Collectively, these results suggest that hypoxia increases the proliferation of ADSCs and enhances the wound-healing function of ADSCs, at least partly, by up-regulating the secretion of VEGF and bFGF.

No abstract

As individuals age, the skin undergoes changes, such as irregular pigmentation, thinning and loss of elasticity, that are due to both genetic and environmental factors. These changes may worsen, progressing to precancerous and cancerous diseases. Various medical treatments and topical cosmeceuticals have been used to treat some symptoms of photoaging, however, the results have been less than satisfactory. Mesenchymal stem cells within the stromal-vascular fraction of subcutaneous adipose tissue, adipose-derived stem cells (ADSCs), display multi-lineage developmental plasticity and secrete various growth factors that control and manage the damaged neighboring cells. Recently, the production and secretion of growth factors has been reported as an essential function of ADSCs, and diverse regenerative effects of ADSCs have been demonstrated in the skin. For example, conditioned medium from ADSCs (ADSC-CM) stimulated both collagen synthesis and migration of dermal fibroblasts, which improved the wrinkling and accelerated wound healing in animal models. ADSC-CM also inhibited melanogenesis in B16 melanoma cells, and protected dermal fibroblasts from oxidative stress induced by chemicals and UVB irradiation. Therefore, ADSCs and soluble factors show promise for the treatment of photoaging, and this review introduces recent research developments of the ADSCs and ADSC-derived secretory factors regarding this issue.

It has been demonstrated that adipose-derived stem cells (ADSCs) secrete cytokines and exhibit diverse pharmacological actions. The present study examined the unknown pharmacological action of ADSCs regarding whitening effects. A conditioned medium of ADSCs (ADSC-CM) was harvested and the whitening effect of ADSC-CM was studied in melanoma B16 cells. ADSC-CM treatment inhibited the synthesis of melanin and the activity of tyrosinase in a dose dependent manner. To clarify the underlying mechanisms of the whitening action of ADSCs, protein levels of melanogenic proteins were measured by Western blot. Although expressions of microphthalmia-associated transcription factor and tyrosinase-related protein 2 (TRP2) remained unchanged, those of tyrosinase and TRP1 were down-regulated. Transforming growth factor-b b1 (TGF-b b1), a potent regulator of melanogenic proteins, was neutralized by the addition of a blocking antibody to ADSC-CM, and down-regulated expression of tyrosinase and TRP1 was almost reversed. Collectively, these results indicate that secretary factors of ADSC inhibit melanin synthesis by down-regulating the expression of tyrosinase and TRP1, which are mainly mediated by TGF-b b1.Key words adipose-derived stem cell; melanin; tyrosinase; tyrosinase-related protein 1 (TRP1); transforming growth factor-b1 (TGF-b1)

We describe a case of malignant proliferating trichilemmal tumor showing multiple distant metastases. For 10 years, the patient had had a round mass in the occiput, which recurred twice after wide excisions, and later metastasized to the cervical lymph nodes, periparotid area, and chest. Each time the lesions were excised, histologic specimens demonstrated a proliferating trichilemmal tumor with increasing nuclear atypia. Serial specimens showed increasing Ki-67 positivity as the extent of the tumor advanced.

Conflicting results have been reported on the association between BsmI restriction fragment length polymorphism (RFLP) at the vitamin D receptor gene (VDR) locus and the clinical response of psoriasis patients to calcitriol or calcipotriol therapy. We evaluated RFLPs of the VDR gene by analyzing the restriction pattern of polymerase chain reaction products in 55 Korean psoriasis patients receiving topical calcipotriol therapy, and evaluated the clinical response. Of the 55 patients, 43 completed the 8-week treatment protocol, and the response was evaluated as excellent in 9 patients, good in 20, and poor in 14. Thus, in our 43 patients BsmI and ApaI polymorphism in the VDR gene did not correlate with response to calcipotriol. The marked predominance of the b allele in the Korean population precludes the possibility that BsmI polymorphism is associated with clinical response to calcipotriol. The pattern of prevalence of the VDR genotypes in the Korean population is very different from that in Western populations. There were no differences in VDR genotype between controls and psoriasis patients at the BsmI site, but there were significant difference in terms of ApaI RFLP as previously reported. In conclusion, polymorphism analysis of the VDR gene with BsmI and ApaI restriction enzymes in psoriasis patients was not helpful in predicting clinical response to calcipotriol.

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A variety of external stimuli are accepted as important in modifying the severity of psoriasis. We sought to determine whether there is any difference in the influence of external factors on psoriasis in relation to extent of involvement or clinical type. A total of 870 psoriasis patients seen between 1982 and 1995 were categorized as mild, moderate, or severe on the basis of extent of the disease, and as guttate, nummular/plaque, or exfoliative/generalized pustular according to clinical type. We then performed a questionnaire survey concerning the influence of external factors such as seasonal changes, sunlight, stress, and pregnancy. These data sets were combined and analysed. The majority of patients stated favorable effects of summer, sunlight, and pregnancy and adverse effects of winter and stress. A statistically significant correlation was noted between the extent of psoriasis and the proportion of patients stating that their disease worsened at times of psychological stress (p < 0.01). We confirmed that psoriasis patients with more extensive involvement experience greater fluctuations in their condition, notice these changes, and therefore relate them to psychological stress.