bims-engexo Biomed News
on Engineered exosomes
Issue of 2025–06–22
five papers selected by
Ravindran Jaganathan, Universiti Kuala Lumpur



  1. Front Immunol. 2025 ;16 1548802
       Purpose: This study aimed to explore the impact of exosomal miRNAs derived from Aspergillus fumigatus (A. fumigatus)-treated human corneal epithelial cells (HCECs) on M1 macrophage activation. We further clarified the mechanisms contributing to M1 macrophage activation in fungal keratitis.
    Methods: Exosomes were harvested from A. fumigatus-treated HCECs. Transmission electron microscopy, particle size analysis, and western blotting were performed to identify exosomes from HCECs. A laser confocal microscope was used to trace the exosomes. Macrophages were incubated with exosomes derived from A. fumigatus-treated HCECs. Global miRNA expression profiling of exosomes was assessed by high-throughput differential gene expression analysis. PCR and western blotting were used to detect the expression of M1-related proteins and SOCS-1. PCR was performed to detect the expression of pro-inflammatory cytokines and let-7b-5p. A dual-luciferase reporter assay was used to confirm the direct targeting of let-7b-5p.
    Results: A. fumigatus-treated HCEC-derived exosomes notably promoted M1 macrophage activation and the production of inflammatory cytokines. Let-7b-5p was overexpressed in exosomes. Let-7b-5p inhibitors suppressed the M1 immune response induced by exosomes. Overexpression of let-7b-5p repressed the expression of SOCS-1, whereas the let-7b-5p inhibitor dramatically increased the expression of SOCS-1. Moreover, a dual-luciferase reporter assay confirmed that SOCS-1 is a direct target of let-7b-5p.
    Conclusions: Let-7b-5p is secreted by A. fumigatus-treated HCECs and transferred to macrophages via exosome secretion. The communication between A. fumigatus-treated HCECs and macrophages was facilitated by exosomal let-7b-5p, resulting in the activation of M1 macrophages. The exosome/let-7b-5p/SOCS-1 axis is vital for innate immunity against fungal keratitis and provides insights into the molecular mechanisms involved in this condition.
    Keywords:  M1 macrophage activation; SOCS-1; exosomes; fungal keratitis; let-7b-5p
    DOI:  https://doi.org/10.3389/fimmu.2025.1548802
  2. Cell Prolif. 2025 Jun 13. e70066
      With the continuous increase of the elderly population and the deepening of population ageing in China, osteoporosis has gradually become one of the significant public health problems. Elucidating the pathophysiological mechanisms that induce osteoporosis and identifying more effective therapeutic targets is of great clinical significance. In this study, in vitro experiments demonstrated that endothelial cell exosomes (EC-EXOs) promoted osteogenic and inhibited adipogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Aged and ovariectomy (OVX)-induced osteoporosis mice models injected with EC-EXOs confirmed that EC-EXOs delayed bone loss. Proteomic analysis revealed a key protein regulating the differentiation of BMSCs. Expression of THBS3 was significantly higher in EC-EXOs than in Human microvascular endothelial cells (HMEC-1). In vitro and in vivo experiments further validated that THBS3 promoted BMSCs' osteogenic differentiation, inhibited their adipogenic differentiation, and retarded bone loss. Computational biology analysis found that CD47 is a downstream target and potentially functional receptor in BMSCs that bind to THBS3. THBS3 treatment of BMSCs down-regulated the expression of CD47 in in vitro experiments. The aged/OVX models further confirmed that EC-EXOs can regulate the differentiation of BMSCs and delay the process of bone loss via the THBS3-CD47 axis. CD47 antibody may be a potential therapeutic agent for treating ageing-associated bone loss.
    Keywords:  CD47 antibody; ageing; bone marrow mesenchymal stem cells; osteogenic differentiation; osteoporosis; thrombospondin‐3; vascular endothelial cell exosomes
    DOI:  https://doi.org/10.1111/cpr.70066
  3. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2025 Jun;41(6): 495-504
      Objective To investigate the effects of exosomes (Exo) derived from high glucose-stimulated glomerular mesangial cells (GMC) on the kidneys of C57BL/6 mice and the intervention mechanism of Tongluo Yishen Formula (TLYSF). Methods The rat GMC were divided into a normal glucose group (NG, with 5.6 mmol/L glucose) and a high glucose group (HG, with 30 mmol/L glucose). After 24 hours of culture, the supernatant was collected, and exosomes were extracted using the ultracentrifugation method. The exosomes were then identified by transmission electron microscopy and Western blot analysis. Male C57BL/6 mice were divided into three groups: NO-Exo group, NG-Exo group, and HG-Exo group. These groups were respectively administered tail vein injections of PBS buffer, exosomes derived from GMC cultured in normal glucose, and exosomes derived from GMC cultured in high glucose, three times a week for a total of 8 weeks. After 8 weeks, the mice in the HG-Exo group were randomly divided into three subgroups: the HG-Exo group [gavaged with saline], the HG-Exo+TLYSF group [gavaged with TLYSF at 34.32 g/(kg.d)], and the HG-Exo + VAL group [gavaged with valsartan suspension at 10.4 mg/(kg.d)], and the intervention lasted for 4 weeks. Urinary microalbumin (mALb), urinary N-acetyl-β-D-aminoglucosidase (NAG), glycated hemoglobin (HbA1c), serum creatinine (Scr) and urea nitrogen (BUN) were detected. Transmission electron microscopy was used to observe the ultrastructure of renal tissues. TUNEL was used to detect the DNA damage of renal tissue cells. Immunofluorescence was used to detect the expression of NOD-like receptor family pyrin domain containing 3 (NLRP3) and wilms tumor 1(WT-1). RT-PCR was used to detect the mRNA levels of NLRP3, cysteinyl aspartate-specific proteinase 1 (caspase-1), interleukin-1 beta (IL-1β), miR-200c-3p and miR-148a-3p. Western Blot was employed to detect the protein expression of NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), caspase-1 and IL-1β. Results Compared with the NG-Exo group, mice in the HG-Exo group exhibited significantly increased levels of mALb, urinary NAG, Scr and BUN. Transmission electron microscopy revealed ruptured podocyte membranes and swollen mitochondria. The positive rate of cells stained by the TUNEL increased, with elevated optical density of NLRP3 and decreased optical density of WT-1. Additionally, there was a significant increase in the level of NLRP3, caspase-1, IL-1β mRNA, as well as miR-200c-3p and miR-148a-3p. The protein expression of NLRP3, ASC, caspase-1, and IL-1β also increased. Compared with HG-Exo group, mice in the HG-Exo+TLYSF group showed decreased levels of mALb, urinary NAG, Scr, and BUN. The podocyte membranes were relatively intact, and mitochondrial damage was alleviated. The positive rate of cells stained by the TUNEL decreased, along with a reduction in the optical density of NLRP3 and an increase in the optical density of WT-1. Furthermore, the mRNA expression levels of NLRP3, caspase-1, IL-1β, miR-200c-3p, and miR-148a-3p were all downregulated to varying degrees. The protein expression levels of NLRP3, ASC, caspase-1, and IL-1β also decreased. Conclusion Exosomes derived from GMC stimulated by high glucose can damage the kidneys of mice and induce podocyte pyroptosis. TLYSF may ameliorate podocyte pyroptosis by downregulating the expression of exosomal miR-200c-3p and miR-148a-3p and inhibiting the activation of the NLRP3/ASC/caspase-1 pathway.
  4. Biochem Biophys Res Commun. 2025 Jun 09. pii: S0006-291X(25)00903-9. [Epub ahead of print]776 152188
      It is well-established that the persistence of human papillomavirus (HPV) infections leads to viral DNA integration into the host genome and has been reported to be associated with the alteration of the exosome cargo contents. More importantly, our previous studies as well as others have demonstrated that the presence of HPV oncoprotein/DNA in exosomes isolated from HPV-positive head and neck cancer (HNC) patients, further supporting a vital role of exosomes in mediating the HPV transmission and carcinogenesis. Here, we reported that proteomic and transcriptomic signatures differed in exosomes derived from HPV-negative and HPV-positive HNC cells, as evidenced by 4D-microDIA quantitative proteomics analysis and small RNA sequencing analysis, respectively. Meanwhile, differential exosomal proteins and miRNAs in exosomes derived from HPV-positive HNC cells were highly clustered with multiple signalling pathways related to HPV infection/viral carcinogenesis. Importantly, receiver operating characteristic (ROC) analysis indicated that the combination of HPV-related proteins (eukaryotic translation initiation factor 2-alpha kinase 2 (EIF2AK2), NF-κB p65 (RELA)) and miRNA (miR-130b) as a panel can discriminate the HPV-positive HNC patients from controls (Area under the curve (AUC) = 0.993, Sensitivity 95 % and Specificity 100 %) as well as between HPV-negative and -positive HNC patients (AUC = 0.781, Sensitivity 81 % and Specificity 67 %) based on the TCGA-HNC dataset. In summary, our findings may offer new insights into the key molecular cargo loading into HPV-enriched exosomes, which could potentially underpin the future design of novel diagnostic and prognostic approaches for predicting HPV-positive HNC.
    Keywords:  Exosome; Head and neck cancer; Human papillomavirus; Proteomics; Transcriptomics
    DOI:  https://doi.org/10.1016/j.bbrc.2025.152188
  5. Am J Reprod Immunol. 2025 Jun;93(6): e70115
       PROBLEM: Recurrent spontaneous abortion (RSA) is defined as two or more consecutive spontaneous abortions in the first 24 weeks of pregnancy. However, the detailed molecular mechanisms behind RSA remain unclear.
    METHOD OF STUDY: We used bioinformatics and systems biology approaches to analyze the underlying molecular mechanisms to provide new insights into the biology of M1 macrophage exosome differentially expressed genes (DEGs) in RSA patients and to identify potential drugs to treat RSA. The trophoblast (HTR-8) was co-cultured with the M1 macrophage exosomes induced by THP-1, and the cell model was constructed for transcriptome sequencing analysis and data source construction. Functional enrichment and pathway analysis of DEGs among the three groups were performed. In addition, differential expression of key genes was verified by RT-qPCR.
    RESULTS: We obtained 172 DEGs from the sequencing data. Metabolic and immune-related pathways and functions are the main pathways of its enrichment. FOCX1, GATA2, YY1, TFAP2A, MEFF2A, and STAT3 are the major transcription factors (TFs) of M1 macrophage exosomes in RSA. Hsa-mir-106b-5p, hsa-mir-149-3p, and hsa-mir-520a-3p are associated with RSA. Finally, the DEGS-disease and DEGS-drug interaction networks are predicted. Gene Ontology (GO) and Kyoto Genome Encyclopedia (KEGG) enrichment analysis revealed clusters and targets associated with maternal and fetal interface immune tolerance in RSA M1 macrophage exosomes.
    CONCLUSIONS: The candidate targets and drugs obtained from M1-type macrophage exosomes in this study may contribute to the effective treatment of RSA.
    Keywords:  M1 macrophage exosomes; differentially expressed genes; drug molecule; recurrent spontaneous abortion; sequencing
    DOI:  https://doi.org/10.1111/aji.70115