Effects of periodontal cells‐derived extracellular vesicles on mesenchymal stromal cell function

Abstract

ObjectiveTo enrich and compare three extracellular vesicles—EV subtypes (apoptotic bodies, microvesicles and small EV) from three periodontal cells (periodontal ligament cells—PDLCs, alveolar bone‐derived osteoblasts—OBs and gingival fibroblasts—GFs), and assess uptake and cell function changes in buccal fat pad‐derived mesenchymal stromal cells (BFP‐MSCs).BackgroundPeriodontal cells such as PDLCs, OBs and GFs have the potential to enhance bone and periodontal regeneration, but face significant challenges, such as the regulatory and cost implications of in vitro cell culture and storage. To address these challenges, it is important to explore alternative ‘cell‐free’ strategies, such as extracellular vesicles which have emerged as promising tools in regenerative medicine, to facilitate osteogenic differentiation and bone regeneration.Methods and MaterialsSerial centrifuges at 2600 and 16 000 g were used to isolate apoptotic bodies and microvesicles respectively. Small EV—sEV was enriched by our in‐house size exclusion chromatography (SEC). The cellular uptake, proliferation, migration and osteogenic/adipogenic differentiation genes were analysed after EVs uptake in BFP‐MSCs.ResultsThree EV subtypes were enriched and characterised by morphology, particle size and EV‐associated protein expression—CD9. Cellular uptake of the three EVs subtypes was observed in BFP‐MSCs for up to 7 days. sEV from the three periodontal cells promoted proliferation, migration and osteogenic gene expression. hOBs‐sEV showed superior levels of osteogenesis markers compared to that hPDLCs‐sEV and hGFs‐sEV, while hOBs‐16k EV promoted adipogenic gene expression compared to that from hPDLCs and hGFs.ConclusionsOur proof‐of‐concept data demonstrate that hOBs‐sEV might be an alternative cell‐free therapeutic for bone tissue engineering.

Understanding exosomes: Part 3—therapeutic + diagnostic potential in dentistry

“…It was found that when the exosomes were cultured with osteogenic differentiation media, osteoblastic differentiation markers, including OCN, OPN and RUNX2, were all upregulated 61 . The study by Han et al 81 . investigated 3 sources of exosomes on buccal fat pad‐derived mesenchymal stromal cells (BFP‐MSCs).…”

“…investigated 3 sources of exosomes on buccal fat pad‐derived mesenchymal stromal cells (BFP‐MSCs). It was concluded that hOBs‐sEVs showed superior levels of osteogenesis markers compared to hPDLCs‐sEVs and hGFs‐sEVs, while hOBs‐16 k EVs promoted adipogenic gene expression compared to hPDLCs and hGFs 81 . In summary, the interest in these studies was characterized by the study by Han et al., demonstrating that various exosomal subsets derived from multiple sources have the ability to impact various cell types differently 81 …”

Insights and Advancements in Periodontal Tissue Engineering and Bone Regeneration

“…Biodegradable materials, such as polyglycolic acid polymers, calcium phosphates ceramics, and certain biodegradable metals, undergo dissolution upon exposure to bodily fluids. Bioinert materials, like titanium, demonstrate stability within the human body and can, under specific circumstances, form both structural and functional connections with adjacent bone (Table 2) [44,46,47]. In tissue engineering, scaffolds play a vital role by maintaining space, storing growth factors, and aiding cell attachment and proliferation when applied to bone defects.…”

“…GFs such as PDGFs, BMPs, IGFs, TGF-β, and VEGFs exhibit considerable potential in bone healing by modulating various cellular behaviors, including recruitment, migration, adhesion, proliferation, and differentiation. A combination of angiogenic factors (VEGF), cell recruiting factors (PDGF), and osteogenic factors (BMPs) has been devised and demonstrated to exert a synergistic effect, proving more advantages for bone repair compared with the administration of any single GF in isolation [45][46][47]. The implementation of growth factors (GFs) via scaffoldbased approaches aims to orchestrate cellular reactions by bridging the communication between cell signaling and the dynamics of bone injury recovery.…”

Orally Derived Stem Cell-Based Therapy in Periodontal Regeneration: A Systematic Review and Meta-Analysis of Randomized Clinical Studies

“…Regenerative medicine commonly employs stem cells, particularly mesenchymal stem cells (MSCs), which possess unique faculties, like self-renewal, clonality, and potency. These adult stem cells exhibit anti-inflammatory properties and contribute to tissue repair processes, secreting mediators with various beneficial effects [28,29]. The expression of specific surface antigens, including CD44, CD73, CD90, and CD105, helps characterize MSCs, while lacking hematopoietic and endothelial markers [30].…”