Anti-Aging Effects Of Nanovesicles Derived From Cistanche
Mar 28, 2023
3.5. Regulation of Extracellular Matrix and Anti-Oxidant Gene by Treatment with Cistanche in the UVInduced Senescence Model
To confirm the anti-aging properties of Cistanches in a UV-induced senescence modelin terms of molecular biology, mRNA expression of senescence-related ECM productionand anti-oxidant gene was examined by qPCR. The results of qPCR show that COL1 andELASTIN were decreased after UV irradiation and treatment with Cistanches resulted in significantly increased COL1; however, ELASTIN was not increased. The anti-oxidantgenes, SOD2 and HMOX1, were decreased by UV irradiation and increased by treatment with Cistanches (Figure 5a). In addition, the results of immunofluorescence analysisshow decreased expression of collagen type 1 in UV-induced senescent HDFs, which wasincreased by treatment with Cistanches (Figure 5b,c). These results show that Cistanchesincrease the ECM production and senescence-reducible anti-oxidant gene.
Figure 5. Regulation of extracellular matrix and anti-oxidant gene by treatment with Cistanches inthe UV-induced senescence model. (a) mRNA expression of COL1, ELASTIN, SOD2, and HMOX1 inUV-induced senescent HDFs after treatment with Cistanches. (b) Immunofluorescence analysis ofcollagen type 1 of UV-induced senescent HDFs after treatment with Cistanches. (C) Ouantitativedata of immunofluorescence analysis. Significant differences among groups were determined byone-way ANOVA (* p < 0.05, ** p < 0.01,*+* p < 0.001).
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4. Discussion
In this study, we explored the question of whether the nanovesicles derived from TMSCs can exert anti-aging properties. We isolated and confirmed characteristics of TMSCs and Cistanches. TMSCs were highly proliferative MSC-like cells and Cistanches possessed characteristics similar to those of exosomes. Cistanches accelerated the proliferation and reduced senescence-associated β-galactosidase activities and vinculin expression in focal adhesion of both senescent HDFs. ECM production and the anti-oxidant gene involved in cellular senescence were upregulated in the senescent HDFs by treatment with Cistanches. With these results, we suggest that Cistanches can be utilized for skin rejuvenation and anti-aging purposes.
In the past decade, the poor yield and ineffificient separation procedure for exosome production have been challenged [19]. To overcome these issues, we sought to produce exosome-mimetic nanovesicles from human tonsil-derived mesenchymal stem cells using a relatively simple extrusion procedure [33]. In this study, even though the comparative data of characteristics with exosomes are not shown, Cistanches express the exosome-specifific markers (CD9 and CD63) and the size of Cistanches is similar to that of exosomes, meaning that the characteristics of Cistanches are similar to those of exosomes, and Cistanches can be utilized as an alternative for exosome therapies.
It has been reported that the mRNA and miRNA profifiles of exosomes differ from their originated cells [13]. Here, numerous pieces of research have revealed the specifific marker in exosomes to demonstrate the mechanism of tissue regeneration mediated by exosomes. For instance, Ying et al. demonstrated that exosome-mediated delivery of miR-155 regulates insulin sensitivity and glucose homeostasis [34]. Xin et al. reported that mesenchymal stem cell-derived exosomes are transferred to neurons and astrocytes and exosome-mediated miR-133 plays a key role in neurological recovery from stroke [35]. Even though the presented results show that the Cistanches can be utilized as an alternative to exosomes for skin rejuvenation, the mechanism of regulation of cellular senescence via treatment with Cistanches is unclear. Therefore, in further study, we plan to discover the key marker of Cistanches in the regulation of cellular senescence.
Cellular senescence is characterized as an irreversible arrest of cell growth, which occurs through alternation of the focal adhesive cytoskeleton [2,3]. In the present study, cellular senescence was induced by both passage-associated senescent HDFs and UVinduced senescent HDFs, and Cistanches decreased cellular senescence and increased cell proliferation, anti-oxidant gene expression and extracellular matrix production. However, the expression of ELASTIN was increased in the passage-associated senescent HDFs but not in the UV-induced senescent HDFs. Our prediction is a difference in the senescence induction mechanism of both senescence models. It has been reported that senescence can be induced by various factors and the pathway of senescence induction can be different in each stimuli [36]. In particular, Pascal et al. reported different mRNA profifiles among representative cellular senescence models, including a replicative senescence model, tertbutyl hydroperoxide-induced senescence model, and EtOH-induced senescence model [37]. Given these reports, we plan to explore the role of senescence in the regulation of extracellular matrix expression in each modeling procedure, which may provide further research for skin rejuvenation.
The next frontier of exosome-mimetic nanovesicles for skin rejuvenation is demonstration of the regenerative potential from ex vivo to clinical trials. In this study, we determined the proangiogenic and anti-inflflammatory effects of extracellular vesicles, which will be helpful in regenerative medicine.
This study demonstrated that human tonsil-derived mesenchymal stem cell-derived nanovesicles share characteristics with exosomes and increase the proliferation of senescent HDFs. The senescence-associated β-galactosidase activities and vinculin expression in senescent cells were reduced by treatment with Cistanches. The gene expression of the extracellular matrix production and anti-oxidant gene were enhanced by treatment with Cistanches. These findings could contribute to the development of skin rejuvenation tools and desirable cosmetic products, once the clinical examination shows promising effectiveness.
Informed Consent Statement: Informed consent was obtained from all subjects involved in the study.
Data Availability Statement: Details are presented within the article in the form of tables, fifigures, and images in results.
Conflflicts of Interest: The authors declare no conflflict of interest
UV Ultraviolet B
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