Umbilical cord mesenchymal stem cell-derived exosomes promote wound healing and skin regeneration via the regulation of inflammation and angiogenesis
Introduction: Wound healing and skin regeneration have become global health challenges, causing substantial harm to the physical and mental health. Many studies have shown that human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-Exos) can promote tissue repair and regeneration. However, the efficacy and underlying mechanisms of hUCMSC-Exos in treatment remain to be elucidated.
Methods: hUCMSC-Exos were isolated by ultracentrifugation and characterized by analyses of nanoparticle tracking analysis (NTA), western blotting (WB), and transmission electron microscopy (TEM). The efficacy of hUCMSC-Exos on the proliferation, migration, and angiogenesis potential of fibroblasts and endothelial cells were examined in vitro. The effects of the hUCMSC-Exos on wound healing were assessed by wound closure rate, histological and immunohistochemical analyses. miRNAs and their target genes that may play a role in skin repair and regeneration were identified and predicted through bioinformatics analysis.
Results: In vitro analysis indicated that hUCMSC-Exos are easily internalized by human umbilical vein endothelial cells (HUVECs) and human skin fibroblasts (HSFs), significantly promoting the proliferation and migration of HSFs, as well as the proliferation and tube formation of HUVECs. Analysis of skin wound models indicated that hUCMSC-Exos significantly accelerate wound healing by reducing inflammation, stimulating angiogenesis, and promoting the formation of extracellular matrix. Mechanistically, bioinformatics analysis suggests that Unc-51-like autophagy activating kinase 2 (ULK2), Collagen Type XIX Alpha 1 Chain (COL19A1), and Interleukin-6 Signal Transducer (IL6ST) are potential key molecules involved in the regulation of wound repair by hUCMSC-Exos.
Discussion: In summary, hUCMSC-Exos regulate the functions of HUVEC and HSFs through miRNA, significantly promoting wound healing and tissue repair, suggesting that hUCMSC Exos therapy is a promising therapeutic approach.
Serum-derived exosomes of young rats protect bone of ovariectomized rats after fatigue loading in vivo
In patients with postmenopausal osteoporosis, the accumulation of bone microdamage further increases fracture risk. Exosomes derived from the circulatory system of young individuals can reverse age-related defects during bone repair. Therefore, the present study aimed to elucidate the mechanisms underlying the protective effects of exosomes against structural degradation under fatigue-induced damage. To this end, a rat tibial fatigue injury model was established to investigate the protective effects of serum-derived exosomes (SDEs) isolated from young rats on bone after fatigue damage. SDEs were administered via intramedullary injection for 3 wk. The results demonstrated that treatment with SDEs significantly alleviated bone microdamage in ovariectomized rats. Specifically, it decreased cortical bone microcrack density and increased the mineral apposition rate significantly. In the distal trabecular bone region, treatment with SDEs increased bone volumetric bone mineral density (vBMD) and decreased trabecular spacing (Tb.Sp) significantly, with no significant changes in the structure model index. This study revealed that SDEs can rapidly repair fatigue-damaged bone microstructure, improving microstructural parameters in non-weight-bearing (distal tibial) cancellous bone (increased vBMD and decreased Tb.Sp). These findings provide a potential novel strategy for early intervention of microdamage in postmenopausal osteoporosis.
Platelet-derived exosomes in situ reprogramming macrophages for rheumatoid arthritis treatment
M1 macrophages secrete various pro-inflammatory cytokines and play a pivotal role in the pathogenesis of rheumatoid arthritis (RA). Therefore, strategies aimed at eliminating synovial M1 macrophages or reprogramming them toward an anti-inflammatory M2 phenotype represent critical approaches for RA treatment. In this study, we propose a novel therapeutic strategy using platelet-derived exosomes (PLT-Exos) to induce the polarization of M1 macrophages into the anti-inflammatory M2 phenotype. Our results demonstrate that PLT-Exos are enriched with immunoregulatory proteins associated with M2 macrophage polarization and can effectively stimulate the conversion of M1 to M2 macrophages. Through phagocytosis assays and in vivo imaging, we confirmed that PLT-Exos are efficiently taken up and specifically accumulate in the joints of collagen-induced arthritis (CIA) mice. Treatment with PLT-Exos significantly reduced joint swelling, arthritis scores and synovial inflammation, while alleviating bone erosion and cartilage damage, leading to marked improvement in motor function in CIA mice. Notably, the therapeutic efficacy of PLT-Exos in RA was comparable to that of the clinical drug methotrexate (MTX), with excellent biocompatibility and no observed cytotoxicity. Overall, the use of PLT-Exos to induce M1-to-M2 macrophage polarization represents a promising therapeutic approach for RA and offers substantial potential for the development of anti-inflammatory treatments for various inflammatory diseases.
Integration of exosome-related genes and differential expression analysis reveals potential biomarkers for prostate cancer
Background
Prostate cancer (PCa) is a prevalent malignancy in men, with exosomes playing a key role in tumor microenvironment and disease progression, yet their molecular mechanisms remain unclear.This study aims to identify potential biomarkers and therapeutic targets in PCa by integrating exosome-related genes with differentially expressed genes (DEGs).
Methods
Four GEO datasets (GSE32448, GSE46602, GSE69223, GSE6956) were analyzed. Batch effects were corrected using the ComBat method, followed by DEG analysis and feature selection via machine learning (LASSO regression, random forest, SVM). Functional enrichment and molecular docking validated the findings.
Results
Post-correction, sample clustering improved significantly. Of 49 overlapping DEGs and exosome-related genes, EEF2, LGALS3, and MYO1D emerged as key biomarkers, with EEF2 showing the highest predictive power (AUC = 0.786). A risk score model achieved an AUC of 0.886. Immune analysis linked these genes to immune cell subsets, and docking studies revealed strong interactions with small molecules like cycloheximide.
Conclusion
This study elucidates the molecular role of exosome-related genes in PCa, proposing predictive biomarkers and novel therapeutic targets, warranting further clinical validation.
