The role and mechanism of engineered nanovesicles derived from hair follicle mesenchymal stem cells in the treatment of UVB-induced skin photoaging.

BACKGROUND: Extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) are effective in the treatment of skin photoaging; however, their low yield and functional decline with passage progression limit their clinical application. Cell-derived nanovesicles (CNVs) are potential alternatives that can address the limitations of EVs derived from MSCs and are conducive to clinical transformations. Hair follicle mesenchymal stem cells (HFMSCs), a type of MSCs, have demonstrated the function of repairing skin tissues; nevertheless, the efficacy of CNVs from HFMSCs (HFMSC-CNVs) in the treatment of skin photoaging remains unclear. Therefore, ultraviolet radiation B (UVB)-induced photoaging nude mice and human dermal fibroblasts (HDFs) were used as experimental models to investigate the therapeutic effects of HFMSC-CNVs in photoaging models. METHODS: HFMSC-CNVs were successfully prepared using the mechanical extrusion method. UVB-induced nude mice and HDFs were used as experimental models of photoaging. Multiple approaches, including hematoxylin-eosin and Masson staining, immunohistochemistry, immunofluorescence, detection of reactive oxygen species (ROS), flow cytometry, western blotting, and other experimental methods, were combined to investigate the possible effects and mechanisms of HFMSC-CNVs in the treatment of skin photoaging. RESULTS: In the nude mouse model of skin photoaging, treatment with HFMSC-CNVs reduced UVB-induced skin wrinkles (p < 0.05) and subcutaneous capillary dilation, alleviated epidermis thickening (p < 0.001), and dermal thinning (p < 0.001). Furthermore, HFMSC-CNVs upregulated proliferating cell nuclear antigen (PCNA) expression (p < 0.05) and decreased the levels of ROS, ß-galactosidase (ß-Gal), and CD86 (p < 0.01). In vitro experiments, treatment with HFMSC-CNVs enhanced the cellular activity of UVB-exposed HDFs (p < 0.05), and reduced ROS levels and the percentage of senescent cells (p < 0.001), and alleviated cell cycle arrest (p < 0.001). HFMSC-CNVs upregulated the expression of Collagen I (Col I), SMAD2/3, transforming growth factor beta (TGF-ß), catalase (CAT), glutathione peroxidase-1 (GPX-1), and superoxide dismutase-1 (SOD-1) (p < 0.05) and downregulated the expression of cycle suppressor protein (p53), cell cycle suppressor protein (p21), and matrix metalloproteinase 3 (MMP3) (p < 0.05). CONCLUSION: Conclusively, the anti-photoaging properties of HFMSC-CNVs were confirmed both in vivo and in vitro. HFMSC-CNVs exert anti-photoaging effects by alleviating cell cycle arrest, decreasing cellular senescence and macrophage infiltration, promoting cell proliferation and extracellular matrix (ECM) production, and reducing oxidative stress by increasing the activity of antioxidant enzymes.

Effects of different stress conditions on the production, bioactivities, physicochemical and structural characteristics of exopolysaccharides synthetized by Schleiferilactobacillus harbinensis Z171.

This study systematically investigated the effects of stress conditions including temperature, pH, H2O2, NaCl, antibiotics on the production and in vitro cholesterol-lowering activity of the exopolysaccharide (EPS) synthetized by Schleiferilactobacillus harbinensis Z171. Additionally, the influences of the optimal stress condition combined with different carbon sources on EPS production were examined, shedding light on the structural characteristics, physicochemical properties and bioactivities of EPSs. The results demonstrated that the EPS produced under H2O2 stress was optimal and presented excellent resistance to simulated gastric juice and α-amylase. Three main fractions, denoted as G-EPS1, F-EPS1 and S-EPS1, were isolated by cellulose DEAE-52 chromatography from crude EPSs synthetized using glucose, fructose and sucrose as carbon sources, respectively. Among them, F-EPS1 possessed the highest cholesterol-lowering, antioxidant and hypoglycemic activities, with the highest molecular weight 91.03 kDa, largest particle size 40.14 nm and apparent viscosity 288.2 mPa·s. Three EPSs exhibited irregular sheet-like and granular structures with good thermal stability. Structural characterization of F-EPS1a (a purified fraction from F-EPS1) revealed that it was a mannan mainly composed of →2)-α-D-Manp-(1→, →3)-α-Manp-(1→ and →2,6)-α-D-Manp-(1→ with branch chains containing α-D-Manp-(1→. F-EPS1a has more potential to be a natural cholesterol-lowering, hypoglycemic and antioxidant supplements in the food industry.