Exosomes Digest (3/4 March 2025)
- Lisa
- Mar 17
- 3 min read
We have collected the most exciting new researches in the field of genetics and cellular research in the past week.
Strontium-boosted exosomes: A new frontier in treating degenerative joint diseases
Temporomandibular joint osteoarthritis (TMJOA) is a debilitating condition that causes severe joint pain, restricted mobility, and progressive cartilage degradation. Despite its significant impact on patients’ quality of life, the underlying pathological mechanisms of TMJOA remain incompletely elucidated, and current therapeutic interventions often provide only limited or transient relief. Exosomes, tiny vesicles released by cells, have garnered attention as potential therapeutic agents due to their role in tissue repair and inflammation modulation. However, challenges such as limited exosome yield and inconsistent therapeutic outcomes have hindered their clinical translation. To overcome these obstacles, researchers have been actively exploring innovative strategies to optimize exosome production and enhance their therapeutic effects.
Mesenchymal cell-derived exosomes and miR-29a-3p mitigate renal fibrosis and vascular rarefaction after renal ischemia reperfusion injury
Background
Renal fibrosis and vascular rarefaction are significant complications of ischemia/reperfusion (I/R) injury. Human umbilical cord mesenchymal cell-derived exosomes (hucMSC-exos) have shown potential in mitigating these conditions. This study investigates the role of miR-29a-3p in exosomes and its therapeutic effects on I/R-induced renal damage.
Methods
Male C57BL/6 mice were subjected to unilateral renal ischemia for 28 min followed by reperfusion. Exosomes and miR-29a-3p mimics/inhibitors were injected into the mice. Renal function, histological analysis, and molecular assays were performed to evaluate fibrosis and vascular integrity.
Results
Exosome treatment significantly improved renal function and reduced fibrosis and vascular rarefaction post-I/R. MiR-29a-3p was highly expressed in hucMSC-exos but reduced in renal fibrosis models. MiR-29a-3p mimic reduced, while its inhibitor exacerbated I/R-induced renal fibrosis and vascular rarefaction. Collagen I and TNFR1 were identified as direct targets of miR-29a-3p in fibroblasts and endothelial cells, respectively. Exosomes overexpressing miR-29a-3p provided superior protection compared to unmodified hucMSC-exos.
Conclusion
HucMSC-exos, particularly those overexpressing miR-29a-3p, have potent therapeutic effects against renal fibrosis and vascular rarefaction post-I/R. MiR-29a-3p targets TNFR1 and collagen I, highlighting its potential in renal fibrosis therapy.
Human Umbilical Cord Mesenchymal Stem Cells-Derived Exosomes Attenuates Experimental Periodontitis in Mice Partly by Delivering miRNAs
Introduction: Periodontitis is the most common non-communicable disease in humans. The main challenge in the treatment of periodontitis is to effectively control periodontal inflammation and promote tissue repair. Human umbilical cord mesenchymal stem cells-derived exosomes (hucMSCs-exo) have been reported to modulate inflammatory responses and promote tissue repairment mainly through miRNAs in several diseases. However, the effect of hucMSCs-exo on periodontitis remains unknown. In this study, we hypothesized that hucMSCs-exo could inhibit bone destruction in periodontitis mice.
Methods: In this study, we constructed and characterized the exo@H drug delivery platform. Lipopolysaccharide was used to construct an inflammatory microenvironment in vitro to detect MC3T3-E1 cells proliferation and bone regeneration capacity. Ligation induced to construct an experimental periodontitis mouse model. The distance of the cement-enamel junction (CEJ) to the alveolar bone crest (ABC) was measured for bone resorption evaluation. Hematoxylin-eosin (H&E) staining and Tartrate resistant acid phosphatase (TRAP) staining were used to observe periodontal tissue changes. MicroRNA (miRNA) sequencing was used to detect differential genes and for bioinformatics analysis. Real-time quantitative polymerase chain reaction (qRT-PCR). WB assay and dual luciferase assay were used to further validate the screened differentially expressed miRNAs and the targeted binding relationship with the corresponding target genes.
Results: We found that lyophilized hucMSCs-exo promoted the proliferation and osteogenic differentiation of MC3T3-E1 cells, and showed more significant proliferative and osteogenic differentiation abilities in combination with the hydrogel (P < 0.05). Using periodontitis mice, bone resorption evaluation revealed a significant reduction in alveolar bone resorption in the exo@H group compared to the hydrogel group (P < 0.01), and exo@H was able to reduce the inflammatory response of periodontal tissues and the number of osteoclasts on the surface of the alveolar bone compared to the hydrogel group. Moreover, 59 miRNAs were upregulated, such as let-7f-5p and miR-203-3p, which positively targeted IL-13 and Nit2, respectively.
Discussion: These results suggest that exo@H provides protection against periodontitis partly by delivering miRNAs to periodontal tissue. Our results confirm the feasibility of the exo@H delivery platform we constructed and the effectiveness of its use for periodontitis treatment, and this study provides a promising approach for the treatment of periodontitis via miRNA.