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Exosomes Digest (2/4 November 2024)

Updated: Nov 20, 2024

We have collected the most exciting new researches in the field of genetics and cellular research in the past week.



Unveiling the promise: Exosomes as game-changers in anti-infective therapy


Extracellular vesicles (EVs)-based intercellular communication (through exosomes, microvesicles, and apoptotic bodies) is conserved across all kingdoms of life. In recent years, exosomes have gained much attention for targeted pharmaceutical administration due to their unique features, nanoscale size, and capacity to significantly contribute to cellular communication. As drug delivery vehicles, exosomes have several advantages over alternative nanoparticulate drug delivery technologies. A key advantage lies in their comparable makeup to the body's cells, which makes them non-immunogenic. However, exosomes vesicles face several challenges, including a lack of an effective and standard production technique, decreased drug loading capacity, limited characterization techniques, and underdeveloped isolation and purification procedures. Exosomes are well known for their long-term safety and natural ability to transport intercellular nucleic acids and medicinal compounds across the blood-brain-barrier (BBB). Therefore, in addition to revealing new insights into exosomes' distinctiveness, the growing availability of new analytical tools may drive the development of next-generation synthetic systems. Herein, light is shed on exosomes as drug delivery vehicles in anti-infective therapy by reviewing the literature on primary articles published between 2002 and 2023. Additionally, the benefits and limitations of employing exosomes as vehicles for therapeutic drug delivery are also discussed.




Exosomes to exosome-functionalized scaffolds: a novel approach to stimulate bone regeneration


Bone regeneration is a complex biological process that relies on the orchestrated interplay of various cellular and molecular events. Bone tissue engineering is currently the most promising method for treating bone regeneration. However, the immunogenicity, stable and cell quantity of seed cells limited their application. Recently, exosomes, which are small extracellular vesicles released by cells, have been found to effectively address these problems and better induce bone regeneration. Meanwhile, a growing line of research has shown the cargos of exosomes may provide effective therapeutic and biomarker tools for bone repair, including miRNA, lncRNA, and proteins. Moreover, engineered scaffolds loaded with exosomes can offer a cell-free bone repair strategy, addressing immunogenicity concerns and providing a more stable functional performance. Herein, we provide a comprehensive summary of the role played by scaffolds loaded with exosomes in bone regeneration, drawing on a systematic analysis of relevant literature available on PubMed, Scopus, and Google Scholar database.




Exosomal non-coding RNAs: Emerging insights into therapeutic potential and mechanisms in bone healing


Exosomes are nano-sized extracellular vesicles (EVs) released by diverse types of cells, which affect the functions of targeted cells by transporting bioactive substances. As the main component of exosomes, non-coding RNA (ncRNA) is demonstrated to impact multiple pathways participating in bone healing. Herein, this review first introduces the biogenesis and secretion of exosomes, and elucidates the role of the main cargo in exosomes, ncRNAs, in mediating intercellular communication. Subsequently, the potential molecular mechanism of exosomes accelerating bone healing is elucidated from the following four aspects: macrophage polarization, vascularization, osteogenesis and osteoclastogenesis. Then, we systematically introduce construction strategies based on modified exosomes in bone regeneration field. Finally, the clinical trials of exosomes for bone healing and the challenges of exosome-based therapies in the biomedical field are briefly introduced, providing solid theoretical frameworks and optimization methods for the clinical application of exosomes in orthopedics.




The role and clinical applications of exosomes in cancer drug resistance


Tumor-secreted exosomes are heterogeneous multi-signal messengers that support cancer growth and dissemination by mediating intercellular crosstalk and activating signaling pathways. Distinct from previous reviews, we focus intently on exosome-therapeutic resistance dynamics and summarize the new findings about the regulation of cancer treatment resistance by exosomes, shedding light on the complex processes via which these nanovesicles facilitate therapeutic refractoriness across various malignancies. Future research in exosome biology can potentially transform diagnostic paradigms and therapeutic interventions for cancer management. This review synthesizes recent insights into the exosome-driven regulation of cancer drug resistance, illuminates the sophisticated mechanisms by which these nanovesicles facilitate therapeutic refractoriness across various malignancies, and summarizes some strategies to overcome drug resistance.




Exosomes Derived from Antler Mesenchymal Stem Cells Promote Wound Healing by miR-21-5p/STAT3 Axis


Background: Deer antlers, unique among mammalian organs for their ability to regenerate annually without scar formation, provide an innovative model for regenerative medicine. This study explored the potential of exosomes derived from antler mesenchymal stem cells (AMSC-Exo) to enhance skin wound healing.


Methods: We explored the proliferation, migration and angiogenesis effects of AMSC-Exo on HaCaT cells and HUVEC cells. To investigate the skin repairing effect of AMSC-Exo, we established a full-thickness skin injury mouse model. Then the skin thickness, the epidermis, collagen fibers, CD31 and collagen expressions were tested by H&E staining, Masson’s trichrome staining and immunofluorescence experiments. MiRNA omics analysis was conducted to explore the mechanism of AMSC-Exo in skin repairing.


Results: AMSC-Exo stimulated the proliferation and migration of HaCaT cells, accelerated the migration and angiogenesis of HUVEC cells. In the mouse skin injury model, AMSC-Exo stimulated angiogenesis and regulated the extracellular matrix by facilitating the conversion of collagen type III to collagen type I, restoring epidermal thickness to normal state without aberrant hyperplasia. Notably, AMSC-Exo enhanced the quality of wound healing with increased vascularization and reduced scar formation. MiRNAs in AMSC-Exo, especially through the miR-21-5p/STAT3 signaling pathway, played a crucial role in these processes.


Conclusion: This study underscores the efficacy of AMSC-Exo in treating skin wounds, suggesting a new approach for enhancing skin repair and regeneration.


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