Abstract
BackgroundThe 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.MethodsHuman 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.ResultsThe 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.ConclusionsThese results indicate that shikimic acid is an effective agent for tissue regeneration.
Highlights
We have recently demonstrated that the protein extract from mouse embryonic stem cells (ESCs) or induced pluripotent stem cells has a potential to convert mouse fibroblasts into iPSCs [1, 2]
We demonstrated that shikimic acid, a major component of Sequoiadendron giganteum (SG) callus extract, could induce mesenchymal-to-epithelial transition (MET) and convert human fibroblast to neural precursor-like skin precursor cells (NeuSKPCs)
Shikimic acid from plant stem cell extract induces dedifferentiation of human somatic cells To investigate whether plant stem cell extract could reprogram somatic cells, we treated Human dermal fibroblast (HDF) with SG callus extract
Summary
We have recently demonstrated that the protein extract from mouse embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs) has a potential to convert mouse fibroblasts into iPSCs [1, 2]. It was not possible to repeatedly obtain this amount per experiment because of the high expenditure of the culture system and batch-to-batch variations To overcome these obstacles, we searched for a compound that could generate stem/progenitor cells with multipotency and allow us to maintain them in an easy and inexpensive way. Calluses are massive growth of cells and accumulation of callose, a plant polysaccharide associated with wounds It can be produced from single undifferentiated cells, which are totipotent, i.e., able to regenerate the whole body of a plant. 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
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