Blanka Maria Borowiec

Regenerative processes occur at various levels in all organisms, yet their complexity continues to raise new questions about their mechanisms. It has been demonstrated that small extracellular vesicles (sEVs), secreted by all cells and influencing their function, play a significant role in regeneration. In the context of regenerative processes, oral mucosal tissues consistently receive interest, as they are among the most rapidly healing tissues in the human body. In this study, we utilized spatial transcriptomics to map gene expression to specific spatial locations within the gingiva tissue section, using publicly available transcriptomic data. This analysis revealed new insights into this tissue and the biogenesis of sEVs within it. The identified clusters encompassed two main regions—the epithelium and lamina propria—as well as minor niches within them. Using Gene Ontology (GO) analysis, we identified two clusters most enriched in extracellular vesicle-related GO processes. These included the superficial and deeper layers of the sulcular epithelium, one of the most peripheral regions of the gingiva. Of the 43 genes identified in the literature as having a potential or documented role in sEVs biogenesis, 12 were selected for further analysis. MUC1, SDCBP2, and VPS37B showed clear specificity and the highest expression in the superficial layer of the sulcular epithelium. CHMP4C also exhibited high expression in this layer, though its levels were comparable to the outer layer of the oral epithelium. Other well-established sEVs marker genes, such as ANXA2, CD9, CD63, CD81, FLOT1, RAB22A, RAB27B, and RAB5A, were also expressed in the examined tissue; however, their expression was not specifically exclusive to the sulcular epithelium. Our study is the first to perform a meta-analysis of available gingival transcriptomic data in the specific context of sEVs biogenesis. The presented data and conclusions provide new insights into the role of different structures within healthy human gingiva and shed new light on both known and potential markers of sEVs biogenesis. These findings may contribute to the development of regeneration-targeted research, especially on oral tissues.

Although ongoing debates persist over the scope of phenomena classified as regenerative processes, the most up-to-date definition of regeneration is the replacement or restoration of damaged or missing cells, tissues, organs, or body parts to full functionality. Despite extensive research on this topic, new methods in regenerative medicine are continually sought, and existing ones are being improved. Small extracellular vesicles (sEVs) have gained attention for their regenerative potential, as evidenced by existing studies conducted by independent research groups. Of particular interest are sEVs derived from the oral mucosa, a tissue renowned for its rapid regeneration and minimal scarring. While the individual regenerative potential of both sEVs and the oral mucosa is somewhat understood, the combined potential of sEVs derived from the oral mucosa has not been sufficiently explored and highlighted in the existing literature. Serving as a broad compendium, it aims to provide scientists with essential and detailed information on this subject, including the nature of the materials employed, isolation and analysis methodologies, and clinical applications. The content of this survey aims to facilitate the comparison of diverse methods for working with sEVs derived from the oral mucosa, aiding in the planning of research endeavors and identifying potential research gaps.

The COVID-19 pandemic is a global challenge, demanding researchers address different approaches in relation to prevention, diagnostics and therapeutics. Amongst the many tactics of tackling these therapeutic challenges, small extracellular vesicles (sEVs) or exosomes are emerging as a new frontier in the field of ameliorating viral infections. Exosomes are part of extracellular vesicles (EVs)—spherical biological structures with a lipid bilayer of a diameter of up to 5000 nm, which are released into the intercellular space by most types of eukaryotic cells, both in physiological and pathological states. EVs share structural similarities to viruses, such as small size, common mechanisms of biogenesis and mechanisms for cell entry. The role of EVs in promoting the viral spread by evading the immune response of the host, which is exhibited by retroviruses, indicates the potential for further investigation and possible manipulation of these processes when tackling the spread and treatment of COVID-19. The following paper introduces the topic of the use of exosomes in the treatment of viral infections, and presents the future prospects for the use of these EVs.