RESUMO
Polydeoxyribonucleotide (PDRN) has the ability to regenerate skin cells and improve the skin barrier and wound healing. This study investigated the possibility of replacing animal-derived PDRN with plant-derived PDRN. To test this, the adventitious roots of Korean ginseng (Panax ginseng C.A. Meyer), which is commonly used to treat various diseases, were suspension-cultivated through tissue culture; subsequently, PDRN was purified using microfluidization, an ultra-high-pressure physical grinding method. The results showed that purified Panax PDRN was effective in healing skin wounds and enhancing the skin barrier. Panax PDRN promoted the proliferation of keratinocytes and fibroblasts by increasing the expression of fibronectin, filaggrin, Ki-67, Bcl-2, inhibin beta A, and Cyclin D1. It also acted as an agonist of the adenosine A2A receptor and induced the phosphorylation of focal adhesion kinase, adenosine triphosphate-dependent tyrosine kinase, and mitogen-activated protein kinase. This activated signal transduction, thereby regenerating skin cells and strengthening the barrier. These results were not only observed in skin cells but also in an artificial skin model (KeraSkinTM). The use of plant-derived PDRN instead of animal-derived PDRN can promote animal welfare and environmental sustainability. Furthermore, Panax PDRN can potentially be a new plant-derived PDRN (PhytoPDRN) that may be utilized in the treatment of various skin diseases.
Assuntos
Panax , Polidesoxirribonucleotídeos , Animais , Polidesoxirribonucleotídeos/farmacologia , Pele , Cicatrização , QueratinócitosRESUMO
Extracellular vesicles (EVs) are secreted from hADSCs in low concentrations, which makes it difficult to utilize them for the development of therapeutic products. To overcome the problem associated with low concentration, we proposed human lactoferrin (hLF) as a stimulant for the secretion of hADSC-derived EVs. hLF has been reported to upregulate intracellular Ca2+, which is known to be capable of increasing EV secretion. We cultured hADSCs in hLF-supplemented media and analyzed the changes in intracellular Ca2+ concentration. The characteristics of hADSC-derived EVs secreted by hLF stimulation were analyzed through their number, membrane protein markers, and the presence of hLFs to EVs. The function of hADSC-derived EVs was investigated through their effects on dermal fibroblasts. We found that hLF helped hADSCs effectively uptake Ca2+, resulting in an increase of EVs secretion by more than a factor of 4. The resulting EVs had enhanced proliferation and collagen synthesis effect on dermal fibroblasts when compared to the same number of hADSC-derived EVs secreted without hLF stimulation. The enhanced secretion of hADSC-derived EVs increased collagen synthesis through enhanced epidermal penetration, which resulted from increased EV numbers. In summary, we propose hLF to be a useful stimulant in increasing the secretion rate of hADSC-derived EVs.