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pharmacodynamic biomarker for vemurafenib treatment in routine. The quantitative real-time RT-PCR in the presented setting represents accurate and reproducible mRNA gene quantification and might improve current staging procedures by stratifying the patients to subpopulations with favourable and unfavourable prognosis. AcknowledgementsThis work was supported by IGA NT 14440-3/2013 Czech Ministry of Health grant. All authors substantially contributed to the manuscript. Petr Arenberger and Monika Arenbergerova designed the research study, performed the research and wrote the manuscript; Alena Fialova and Spyridon Gkalpakiotis performed the research and analysed the data; and Andrea Pavlikova performed the research. The submitted and final version of the manuscript was critically revised and approved by the authors. Conflict of interestThe authors have declared no conflicting interests. Supporting InformationAdditional Supporting Information may be found online in the supporting information tab for this article:Data S1. Extended information on experimental methods.

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Background The human skin-derived precursors (SKPs) are a good cell source for regeneration. However, the isolation of SKP from human skin is limited. To overcome this drawback, we hypothesized that the component of plant stem cells could convert human fibroblasts to SKPs. Methods Human dermal fibroblasts were treated with shikimic acid, a major component of Sequoiadendron giganteum callus extract. The characteristics of these reprogrammed cells were analyzed by qPCR, western blot, colony-forming assay, and immunofluorescence staining. Artificial human skin was used for CO2 laser-induced wound experiments. Human tissues were analyzed by immunohistochemistry. Results The reprogrammed cells expressed nestin (a neural precursor-specific protein), fibronectin, and vimentin and could differentiate into the ectodermal and mesodermal lineage. Nestin expression was induced by shikimic acid through the mannose receptor and subsequent MYD88 activation, leading to P38 phosphorylation and then CREB binding to the nestin gene promoter. Finally, we confirmed that shikimic acid facilitated the healing of cut injury and enhanced dermal reconstruction in a human artificial skin model. Moreover, in a clinical study with healthy volunteers, plant callus extracts increased the expression of stem cell markers in the basal layer of the epidermis and collagen deposit in the dermis. Conclusions These results indicate that shikimic acid is an effective agent for tissue regeneration.