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Plant callus-derived shikimic acid regenerates human skin through converting human dermal fibroblasts into multipotent skin-derived precursor cells

Cited 2 time in Web of Science Cited 3 time in Scopus
Issue Date
2021-06-11
Publisher
BMC
Citation
Stem Cell Research & Therapy. 2021 Jun 11;12(1):346
Keywords
Shikimic acidCell reprogrammingNeural precursorSkin-derived precursorSingle chemical-derived trans-differentiation
Abstract
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.
ISSN
1757-6512
Language
English
URI
https://hdl.handle.net/10371/174792
DOI
https://doi.org/10.1186/s13287-021-02409-3
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Graduate School of Convergence Science and Technology (융합과학기술대학원)Dept. of Molecular and Biopharmaceutical Sciences (분자의학 및 바이오제약학과)Journal Papers (저널논문_분자의학 및 바이오제약학과)
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