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

Stem Cell Research & Therapy

Shin-Hyae Lee¹  Jin Hur²  Beom Joon Kim³  Won-Seok Park⁴  Ah-Reum Kim⁴  Hyun-Jai Cho⁵  Han-Mo Yang⁵  Hyunduk Jang⁵  Yoo-Wook Kwon⁵  Hyo-Soo Kim⁶ 

[1] Clinical Research Team, SK Chemical, Life Science Biz., Gyeonggi-do, 13494, Seongnam-si, Republic of Korea;Department of Convergence Medicine, Pusan National University School of Medicine, 50612, Yangsan, Korea;Departments of Dermatology, Chung-Ang University College of Medicine, Seoul, Republic of Korea;Skin Research Division, AMOREPACIFIC Corp. R&D Unit, -si, Gyeonggi-do, Yongin, Republic of Korea;Strategic Center of Cell and Bio Therapy for Heart, Diabetes & Cancer, Biomedical Research Institute, Seoul National University Hospital, 03080, Seoul, Republic of Korea;Strategic Center of Cell and Bio Therapy for Heart, Diabetes & Cancer, Biomedical Research Institute, Seoul National University Hospital, 03080, Seoul, Republic of Korea;Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, 03080, Seoul, Republic of Korea;Cardiovascular Center & Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea;

关键词: Shikimic acid;    Cell reprogramming;    Neural precursor;    Skin-derived precursor;    Single chemical-derived trans-differentiation;   

DOI  :  10.1186/s13287-021-02409-3

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY