Biology subjects

des Rieux, A.

Publications and source records attributed to des Rieux, A..

4 recordsLinked to original sources

bioRxiv2026

Goat Milk-derived Extracellular Vesicles modulate glial responses in vitro and attenuate neuroinflammation in vivo

Milk-derived extracellular vesicles (MEV) represent a naturally derived, potentially scalable platform for immunomodulation, yet their effects on central nervous system (CNS) glial inflammation at defined particle-to-cell ratios remain insufficiently characterized. Here, we investigated the immunomodulatory effects of goat milk-derived MEV in cellular and murine models of neuroinflammation. MEV-enriched preparations were obtained by sequential filtration, ultrafiltration, and size-exclusion chromatography, and characterized by scanning electron microscopy, nanoparticle tracking analysis, and dynamic light scattering. In LPS-stimulated BV2 microglia-like cells, MEV at 250 and 2500 particles per cell significantly reduced CD40 expression. In primary rat mixed glial cultures, microglia, astrocytes, and oligodendrocytes internalized MEV. At 250 particles per cell, MEV significantly reduced CD40 and IL1{beta} gene expression at the mixed-culture level. In both cellular models, MEV also increased markers associated with an M2-like microglial phenotype under resting conditions. Following intrathecal administration in healthy mice, MEV did not induce significant changes in the inflammatory gene markers assessed at 8 h. In an LPS-induced mouse model of neuroinflammation, intrathecal MEV administration reduced CD40 protein expression towards control levels within 24 h and shifted the inflammatory marker profile towards a pro-resolutive state, as indicated by increased Arg1 levels and elevated CD206/CD86 and IL10/IL6 ratios. These findings identify goat milk-derived MEV-enriched preparations as potential modulators of CNS glial inflammation and support further investigation of their therapeutic potential.

neuroscience↗

bioRxiv2026

Advanced microfluidic strategy for In-Bead MSC spheroid formation and co-encapsulation of necrosis inhibitor-loaded nanoparticles

Mesenchymal stem/stromal cells (MSCs) are key players in regenerative medicine due to their immunomodulatory properties and ability to promote tissue repair. However, their therapeutic efficacy is often limited by rapid clearance following transplantation. MSC spheroids have shown enhanced functional properties, and we hypothesize that encapsulating them within hydrogel microbeads could offer additional protection and improve their viability. In this study, we developed a novel droplet-based microfluidic protocol for human MSCs derived from the apical papilla (SCAP) encapsulation and In-Bead spheroid formation within alginate microbeads. Optimization of the protocol allowed the formation of MSC spheroids in alginate droplets overnight (In-Bead), before alginate cross-linking and retrieval of alginate beads loaded with MSC spheroids. SCAP were successfully encapsulated within 275 {micro}m alginate microbeads, forming spheroids of approximately 80 {micro}m in diameter. Encapsulated SCAP spheroids retained their immunomodulatory properties. The process was further optimized by incorporating nanomedicines into the alginate solution before the formation of droplets and then spheroids, forming thus hybrid beads (Sph.Beads/NP). Nanomedicines were loaded with NecroX-5, a necrosis inhibitor, to improve SCAP viability further. Live/Dead assays indicated a protective effect of the nanomedicines, supporting the potential of this system for advanced cell delivery in regenerative applications. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=150 SRC="FIGDIR/small/732109v1_ufig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@1625a4eorg.highwire.dtl.DTLVardef@16c6faorg.highwire.dtl.DTLVardef@161819aorg.highwire.dtl.DTLVardef@83c0d7_HPS_FORMAT_FIGEXP M_FIG C_FIG Graphical abstractA combination strategy enhancing MSC viability through spheroid formation, microencapsulation, and nanomedicine association achieved by microfluidic encapsulation with In-Bead spheroid formation. Created with BioRender

bioengineering↗

bioRxiv2024

Nanoparticles loaded with a CSF1R antagonist selectively depletes microglial cells and modulates inflammation in spinal cord injury

Neuroinflammation is a principal event occurring after spinal cord injury (SCI). M1-like microglia are key players in the inflammatory response after injury. We hypothesize that the depletion of this microglia subtype would result in a more pro-resolutive environment, favorable to SCI repair. The colony-stimulating factor 1 receptor (CSF1R) antagonist PLX5622 has been used to deplete microglia in the central nervous system. Although PLX5622 can freely cross the blood-brain barrier after systemic administration, the low drug concentration within the SCI site hampers its effectiveness. Additionally, systemic administration of PLX5622 in the scope of SCI treatment can induce side effects due to off-target accumulation. In this study, we specifically depleted M1- like microglia by designing polymeric nanoparticles loaded with PLX5622 (PLX NPs) to locally treat spinal cord contusion. PLX NP was prepared using a microfluidic-assisted approach showing high encapsulation efficiency (approx. 84%), nanosized dimensions (100 nm), and batch-to-batch reproducibility. PLX NP displayed selective activity in depleting M1-like microglial cells in both resting and lipopolysaccharide (LPS)-activated mixed microglial cell models compared with the free drug counterparts while preserving non-targeted glial cells. Furthermore, locally administered PLX NP downregulated proinflammatory cytokines (e.g., TNF-, IL-6, and IL-1{beta}), increasing the M2/M1-like microglia ratio, thus reducing inflammation in a SCI contusion model. Our data support the hypothesis that local treatment with PLX NPs, a formulation with a high translational value, reduces neuroinflammation, with potential applications in SCI and central nervous system inflammatory diseases. Graphical abstract. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=184 SRC="FIGDIR/small/624647v1_ufig1.gif" ALT="Figure 1000"> View larger version (55K): org.highwire.dtl.DTLVardef@1bfd912org.highwire.dtl.DTLVardef@446923org.highwire.dtl.DTLVardef@1527c0borg.highwire.dtl.DTLVardef@4df259_HPS_FORMAT_FIGEXP M_FIG The colony-stimulating factor 1 receptor (CSF1R) antagonist PLX5622 loaded in polymeric nanoparticles (PLX NP) is delivered for the treatment of neuroinflammation in spinal cord injury. C_FIG

neuroscience↗

bioRxiv2019

Decreased viability and neurite length in neural cells treated with chitosan-dextran sulfate nanocomplexes

CXCL12 is a chemokine known to regulate migration, proliferation, and differentiation of neural stem cells (NSCs) and to play a neuroprotective role in ischemic stroke. Chitosan-dextran sulfate nanocomplexes (Ch/DS NC) are known nanoparticulated systems used to efficiently deliver heparin-binding factors. Here we evaluate Ch/DS NC as carriers for CXCL12 in a mouse model of stroke. Free CXCL12 reduced the size of the ischemic brain lesion. However, when Ch/DS NC were administrated, the stroke volume increased. Neurotoxic screening revealed that Ch/DS NC reduced neuronal viability, decreased the extension of neurites and impaired NSC migration in vitro. To the best of our knowledge, neurotoxicity of Ch/DS NC has not been reported and further screenings will be needed in order to evaluate the biological safety of these nanocomposites. Our results add new data on nanoparticle neurotoxicity and may help us to better understand the complex interactions of the nanostructures with biological components.

neuroscience↗