Mesenchymal stem/stromal cells (MSCs) are promising tools in cell therapy. They secrete extracellular vesicles (EVs) that carry different classes of molecules that can promote skin repair, but the mechanisms are poorly understood. Skin wound healing is a complex process that requires the activity of several signaling pathways and cell types, including keratinocytes and fibroblasts. In this study, we explored whether adipose tissue MSC-derived EVs could accelerate migration and proliferation of keratinocytes and fibroblasts, activate the AKT pathway, and promote wound healing in vivo. Furthermore, we evaluated if EV effects are miR-205 dependent. We found that MSC EVs had an average diameter of 135 nm. Keratinocytes and fibroblasts exposed to EVs exhibited higher levels of proliferation, migration, and AKT activation. Topical administration of EVs accelerated skin wound closure. Knockdown of miR-205 decreased AKT phosphorylation in fibroblasts and keratinocytes, whereas migration was decreased only in keratinocytes. Moreover, knockdown of miR-205 failed to inhibit AKT phosphorylation in fibroblasts and keratinocytes exposed to EVs. About the mechanism of EV effects, we found that incubation with EVs prevented inhibition of AKT activation by miR-205 knockdown, suggesting that EVs activate AKT independently of miR-205. In conclusion, we demonstrated that EVs are a promising tool for wound healing.
Currently, nanostructured compounds have been standing out for their optical, mechanical, and chemical features and for the possibilities of manipulation and regulation of complex biological processes. One of these compounds is boron nitride nanotubes (BNNTs), which are a nanostructured material analog to carbon nanotubes, but formed of nitrogen and boron atoms. BNNTs present high thermal stability along with high chemical inertia. Among biological applications, its biocompatibility, cellular uptake, and functionalization potential can be highlighted, in addition to its eased utilization due to its nanometric size and tumor cell internalization. When it comes to new forms of therapy, we can draw attention to boron neutron capture therapy (BNCT), an experimental radiotherapy characterized by a boron-10 isotope carrier inside the target and a thermal neutron beam focused on it. The activation of the boron-10 atom by a neutron generates a lithium atom, a gamma ray, and an alpha particle, which can be used to destroy tumor tissues. The aim of this work was to use BNNTs as a boron-10 carrier for BNCT and to demonstrate its potential. The nanomaterial was characterized through XRD, FTIR, and SEM. The WST-8 assay was performed to confirm the cell viability of BNNTs. The cells treated with BNNTs were irradiated with the neutron beam of a Triga reactor, and the apoptosis caused by the activation of the BNNTs was measured with a calcein AM/propidium iodide test. The results demonstrate that this nanomaterial is a promising candidate for cancer therapy through BNCT.
In this study, we report the production of a mesoporous silica/hydroxyapatite‐based nanocomposite containing copper (Cu) functionalized with methacrylic acid (MAA), a pH‐sensitive polymer. The functionalization of the nanoparticles surface was performed using the microwave method in order to anchor the cross‐linking tetraethylene glycol dimethacrylate (TEGDMA), onto the nanoparticles surface followed by MAA polymerization. The materials were characterized by XRD, XRF spectroscopy, scanning and transmission electron microscopy, Fourier transform infrared spectroscopy, thermal analysis, zeta potential, and elemental analysis. Studies of the incorporation and release of the antitumor methotrexate drug were performed in order to evaluate the potential use of these drug carrier systems in cancer therapy. Moreover, the in vitro cytotoxicity of the samples in fibroblast and SAOS‐2 cells was investigated, and the activity of the adipose‐derived stem cell alkaline phosphatase on nanocomposites was studied by in vitro assays. The results indicate that the Cu‐containing nanocomposites can be easily produced and that these compositions have beneficial effects in stem cells, maintaining cell viability, and allowing alkaline phosphatase expression. In conclusion, data from this work show that the nanocomposites obtained have adequate characteristic to be used as drug delivery platform. Furthermore, the biomaterial is a promising structure for treatment of bone tumor.
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