Nanoparticles of Bioactive Glass Enhance Biodentine Bioactivity on Dental Pulp Stem Cells.

This study aimed to investigate the cytotoxicity and bioactivity of a novel nanocomposite containing nanoparticles of bioactive glass (nBGs) on human dental pulp stem cells (hDPSCs). nBGs were synthesized by the sol-gel method. Biodentine (BD) nanocomposites (nBG/BD) were prepared with 2 and 5% wt of nBG content; unmodified BD and glass ionomer cement were used as references. Cell viability and attachment were evaluated after 3, 7 and 14 days. Odontogenic differentiation was assessed with alkaline phosphatase (ALP) activity after 7 and 14 days of exposure. Cells successfully adhered and proliferated on nBG/BD nanocomposites, cell viability of nanocomposites was comparable with unmodified BD and higher than GIC. nBG/BD nanocomposites were, particularly, more active to promote odontogenic differentiation, expressed as higher ALP activity of hDPSCs after 7 days of exposure, than neat BD or GIC. This novel nanocomposite biomaterial, nBG/BD, allowed hDPSC attachment and proliferation and increased the expression of ALP, upregulated in mineral-producing cells. These findings open opportunities to use nBG/BD in vital pulp therapies.

Astrocyte-Derived Small Extracellular Vesicles Regulate Dendritic Complexity through miR-26a-5p Activity.

In the last few decades, it has been established that astrocytes play key roles in the regulation of neuronal morphology. However, the contribution of astrocyte-derived small extracellular vesicles (sEVs) to morphological differentiation of neurons has only recently been addressed. Here, we showed that cultured astrocytes expressing a GFP-tagged version of the stress-regulated astrocytic enzyme Aldolase C (Aldo C-GFP) release small extracellular vesicles (sEVs) that are transferred into cultured hippocampal neurons. Surprisingly, Aldo C-GFP-containing sEVs (Aldo C-GFP sEVs) displayed an exacerbated capacity to reduce the dendritic complexity in developing hippocampal neurons compared to sEVs derived from control (i.e., GFP-expressing) astrocytes. Using bioinformatics and biochemical tools, we found that the total content of overexpressed Aldo C-GFP correlates with an increased content of endogenous miRNA-26a-5p in both total astrocyte homogenates and sEVs. Notably, neurons magnetofected with a nucleotide sequence that mimics endogenous miRNA-26a-5p (mimic 26a-5p) not only decreased the levels of neuronal proteins associated to morphogenesis regulation, but also reproduced morphological changes induced by Aldo-C-GFP sEVs. Furthermore, neurons magnetofected with a sequence targeting miRNA-26a-5p (antago 26a-5p) were largely resistant to Aldo C-GFP sEVs. Our results support a novel and complex level of astrocyte-to-neuron communication mediated by astrocyte-derived sEVs and the activity of their miRNA content.