Inflammation-driven tissue damage poses significant challenges in dental regeneration, particularly in conditions like pulpitis. This study explores the intricate interplay between stem cells from the apical papilla (SCAP), their extracellular vesicles (sEVs), and immune cells under inflammatory stress. Leveraging lipopolysaccharide (LPS) as an inflammatory trigger, we isolated and characterized sEVs from SCAP (SEVs-LPS), uncovering their pivotal role in modulating macrophage polarization and osteoblast differentiation.
Our findings reveal that SEVs-LPS amplify the pro-inflammatory M1 macrophage phenotype, marked by elevated cytokine secretion (IL-6, IL-1β), while diminishing anti-inflammatory M2 markers (IL-10, CD206). This inflammatory polarization impairs the mineralization potential of SCAP, a critical factor in bone regeneration. Interestingly, despite their reduced protein content compared to control vesicles, sEVs-LPS demonstrated robust immunomodulatory effects, highlighting their potential as key mediators of the inflammatory microenvironment.
Through cutting-edge techniques, including tunable resistive pulse sensing, electron microscopy, and advanced gene expression assays, this study provides a comprehensive profile of SEVs-LPS. These vesicles exhibit a diameter of approximately 100 nm, characteristic of exosome-like morphology, and express hallmark vesicular markers (CD9, CD63, CD81, HSP70). Crucially, while SEVs-LPS diminished osteogenic outcomes, they retained their capacity to influence immune responses, underscoring a dual-edged role in regeneration and inflammation.
By elucidating the dynamic crosstalk between SCAP-derived vesicles and immune cells, this research opens new avenues for therapeutic strategies targeting inflammation resolution. Tailoring sEVs to mitigate pro-inflammatory effects or enhance regenerative properties may hold the key to advancing pulp and bone regeneration therapies. These insights not only deepen our understanding of oral immunology but also position sEVs as potential vectors for novel anti-inflammatory and pro-regenerative treatments.
This study invites to rethink the role of extracellular vesicles in inflammatory contexts and their transformative potential in regenerative dentistry.