We have collected the most exciting new researches in the field of genetics and cellular research in the past week.
Exosomes in Oral Diseases: Mechanisms and Therapeutic Applications
Exosomes, small extracellular vesicles secreted by various cells, play crucial roles in the pathogenesis and treatment of oral diseases. Recent studies have highlighted their involvement in orthodontics, periodontitis, oral squamous cell carcinoma (OSCC), and hand, foot, and mouth disease (HFMD). Exosomes have a positive effect on the inflammatory environment of the oral cavity, remodeling and regeneration of oral tissues, and offer promising therapeutic options for bone and periodontal tissue restoration. In OSCC tumor-derived exosomes promote cancer progression through cell proliferation, migration, invasion, and angiogenesis, and serve as potential biomarkers for early diagnosis and prognosis. Additionally, engineered exosomes constructed specifically based on exosome properties hold great promise for targeted drug delivery and regenerative therapies such as bone regeneration in orthodontics and periodontal healing. With continued research, exosomes hold great potential for improving diagnosis and treatment in oral diseases, advancing personalized and regenerative therapies.
Exosomes Derived from Apelin-Pretreated Mesenchymal Stem Cells Ameliorate Sepsis-Induced Myocardial Dysfunction by Alleviating Cardiomyocyte Pyroptosis via Delivery of miR-34a-5p
Background: Exosomes sourced from mesenchymal stem cells (MSC-EXOs) have become a promising therapeutic tool for sepsis-induced myocardial dysfunction (SMD). Our previous study demonstrated that Apelin pretreatment enhanced the therapeutic benefit of MSCs in myocardial infarction by improving their paracrine effects. This study aimed to determine whether EXOs sourced from Apelin-pretreated MSCs (Apelin-MSC-EXOs) would have potent cardioprotective effects against SMD and elucidate the underlying mechanisms.
Methods: MSC-EXOs and Apelin-MSC-EXOs were isolated and identified. Mice neonatal cardiomyocytes (NCMs) were treated with MSC-EXOs or Apelin-MSC-EXOs under lipopolysaccharide (LPS) condition in vitro. Cardiomyocyte pyroptosis was determined by TUNEL staining. RNA sequencing was used to identify differentially expressed functional miRNAs between MSC-EXOs and Apelin-MSC-EXOs. MSC-EXOs and Apelin-MSC-EXOs were transplanted into a mouse model of SMD induced by cecal ligation puncture (CLP) via the tail vein. Heart function was evaluated by echocardiography.
Results: Compared with MSC-EXOs, Apelin-MSC-EXO transplantation greatly enhanced cardiac function in SMD mice. Both MSC-EXOs and Apelin-MSC-EXOs suppressed cardiomyocyte pyroptosis in vivo and in vitro, with the latter exhibiting superior protective effects. miR-34a-5p effectively mediated Apelin-MSC-EXOs to exert their cardioprotective effects in SMD with high mobility group box-1 (HMGB1) as the potential target. Mechanistically, Apelin-MSC-EXOs delivered miR-34a-5p into injured cardiomyocytes, thereby ameliorating cardiomyocyte pyroptosis via regulation of the HMGB1/AMPK axis. These cardioprotective effects were partially abrogated by downregulation of miR-34a-5p in Apelin-MSC-EXOs.
Conclusion: Our study revealed miR-34a-5p as a key component of Apelin-MSC-EXOs that protected against SMD via mediation of the HMGB1/AMPK signaling pathway.
Exosomes and Exosome-Mimetics for Atopic Dermatitis Therapy
Exosomes and exosome mimetics are used as alternatives to cell therapy. They have shown potential in treating skin disorders by fortifying the skin barrier, mediating angiogenesis, and regulating the immune response while minimizing side effects. Currently, numerous studies have applied exosome therapy to treat atopic dermatitis (AD) caused by a weakened skin barrier and chronic inflammation. Research on exosomes and exosome mimetics represents a promising avenue for tissue regeneration, potentially paving the way for new therapeutic options. However, the efficacy of the therapy remains poorly understood. Also, the potential of exosome mimetics as alternatives to exosomes in skin therapy remains underexplored. Here, we reviewed the pathological features and current therapies of AD. Next, we reviewed the application of exosomes and exosome mimetics in regenerative medicine. Finally, we highlighted the therapeutic effects of exosomes based on their cell source and assessed whether exosome mimetics are viable alternatives. Exosome therapy may treat AD due to its skin regenerative properties, and exosome mimetics may offer an equally effective yet more efficient alternative. Research on exosomes and exosome mimetics represents a promising avenue for tissue regeneration, potentially paving the way for new therapeutic options.