Gábor Szabad

In Vitro Dedifferentiation of Melanocytes from Adult Epidermis

In previous work we described a novel culture technique using a cholera toxin and PMA-free medium (Mel-mix) for obtaining pure melanocyte cultures from human adult epidermis. In Mel-mix medium the cultured melanocytes are bipolar, unpigmented and highly proliferative. Further characterization of the cultured melanocytes revealed the disappearance of c-Kit and TRP-1 and induction of nestin expression, indicating that melanocytes dedifferentiated in this in vitro culture. Cholera toxin and PMA were able to induce c-Kit and TRP-1 protein expressions in the cells, reversing dedifferentiation. TRP-1 mRNA expression was induced in dedifferentiated melanocytes by UV-B irradiated keratinocyte supernatants, however direct UV-B irradiation of the cells resulted in further decrease of TRP-1 mRNA expression. These dedifferentiated, easily accessible cultured melanocytes provide a good model for studying melanocyte differentiation and possibly transdifferentiation. Because melanocytes in Mel-mix medium can be cultured with human serum as the only supplement, this culture system is also suitable for autologous cell transplantation.

The altered expression of syndecan 4 in the uninvolved skin of venous leg ulcer patients may predispose to venous leg ulcer.

Syndecan 4 (SDC4), a heparan sulfate proteoglycan, and neuropilin 1 (NRP1), a transmembrane receptor, are both involved in normal wound healing, but little is known about their possible role in venous leg ulcer pathogenesis. We aimed to investigate whether there are any expression abnormalities and/or gene polymorphisms of SDC4 and NRP1 associated with venous leg ulcer. SDC4 showed significantly lower mRNA and protein expression in the uninvolved dermis of venous leg ulcer patients (n=15) compared with controls (n=15; p=0.0136), while NRP1 showed no expression abnormalities. None of the examined SDC4 and NRP1 polymorphisms showed a difference in their allelic distribution between leg ulcer patients (n=92) and controls (n=92). We hypothesize that SDC4 may play an essential role not only in the inflammation and tissue formation phases of normal wound healing, but its expression abnormalities observed in the uninvolved dermis of venous leg ulcer patients may contribute to venous leg ulcer development.

Chronic Nonhealing Wounds: Could Leg Ulcers Be Hereditary?

Background. A number of well-known acquired and putative inherited etiological factors contribute to the development of venous leg ulcer (VLU). Aim. In this study we set out to perform a meta-analysis of putative genetic and acquired factors predisposing to VLU development. Methods. VLU patients () were divided into three subgroups in accordance with their acquired etiological factors. The frequencies of four genetic factors were determined: the R506Q (Leiden) mutation of the F5 gene, the G20210A mutation of the F2 (prothrombin) gene, the 2451 A/G SNP of the fibroblast growth factor receptor 2 (FGFR2) 3′ UTR, and the −308 G/A SNP of the tumor necrosis factor α (TNFA) promoter. Results. The −308 TNFA SNP exhibited a higher frequency among VLU patients without known acquired predisposing factor in their history, than among patients with thrombosis or soft tissue infection in their history (Fisher ). Conclusions. This study has demonstrated that the group of VLU patients is heterogeneous in their genetic predisposing factors. Further large-scale studies are needed to delineate the associations among genetic and acquired etiological factors with regard to VLU development and to integrate the consequences of the already known genetic factors to the management of VLU.