Biology subjects

Delila, L.

Publications and source records attributed to Delila, L..

4 recordsLinked to original sources

bioRxiv2026

IgA/IgM chromatographic depletion enables efficient 20-nm virus nanofiltration of mini-pool caprylic-acid IgG

Global shortages of human plasma-derived immunoglobulin G (IgG) remain a major challenge for treating primary immunodeficiencies, especially in low- and middle-income countries. Ensuring virus safety is essential, and nanofiltration provides robust removal of small, non-enveloped viruses. We examined whether removing immunoglobulin A (IgA) and immunoglobulin M (IgM) by anion-exchange chromatography improves the performance of 20-nm nanofiltration applied to small-pool caprylic acid-purified IgG. Cryo-poor plasma was treated with 5% caprylic acid at pH 5.5, concentrated by ultrafiltration, and processed on Fractogel TMAE to deplete IgA and IgM. The IgG flow-through was filtered sequentially through Planova 35N and 20N (or S20N) filters. Direct nanofiltration of caprylic acid-treated IgG with residual IgA and IgM led to rapid membrane clogging and low throughput. Depletion of IgA and IgM increased filtration capacity more than threefold and stabilized flux. Dynamic light scattering confirmed the predominance of monomeric IgG and absence of aggregates after chromatography and nanofiltration. Overall, this process combines two complementary virus reduction steps, caprylic acid treatment and nanofiltration, and provides a practical option for LMICs to convert available domestic plasma into IgG; it could also be adapted to the manufacture of hyperimmune or convalescent IgG preparations.

bioengineering↗

bioRxiv2025

Human Platelet-derived Lysates and Extracellular Vesicles Restore Mitochondrial Function and Redox Balance in Neuronal Models

Platelet-derived biomaterials are emerging as promising cell-free therapeutic platforms for regenerative medicine and neurorestoration. Among them, human platelet pellet lysates (HPPL) and platelet-derived extracellular vesicles (PEVs), prepared from clinical-grade allogeneic platelet concentrates, provide two complementary biomaterial formats: a soluble trophic factor-rich lysate and a vesicular formulation enriched in bioactive cargo. Because mitochondrial dysfunction and redox imbalance are hallmarks of neurodegeneration, we investigated whether these platelet-derived biomaterials could protect against rotenone-induced mitochondrial injury. HPPL and PEVs were bioprocessed from clinical-grade platelet concentrates and characterized for protein content, antioxidant capacity, vesicle morphology, size distribution, concentration and platelet and EVs markers. Differentiated N2A and SH-SY5Y neuronal cells were pretreated with 5% v/v HPPL or PEVs before rotenone (5 {micro}M) exposure, while zebrafish embryos received 20 g/mL HPPL or PEVs before rotenone (200 nM) challenge. Both biomaterials restored ATP production, reduced reactive oxygen species (ROS), preserved mitochondrial membrane potential and ultrastructure, and improved neuronal survival. They also normalized key markers of mitochondrial biogenesis and dynamics, including peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1), mitofusin-1 (MFN1), and dynamin-related protein 1 (DRP1). Proteomic analyses further showed enrichment of mitochondrial-associated antioxidant and metabolic proteins in HPPL and PEVs, and revealed restoration of oxidative phosphorylation, tricarboxylic acid cycle-related pathways, antioxidant defense, and mitochondrial dynamics in rotenone-injured cells following pretreatment. In zebrafish embryos, both biomaterials improved survival and hatching, reduced developmental abnormalities and oxidative stress, and preserved mitochondrial ultrastructure. These findings identify HPPL and PEVs as platelet-derived biomaterials with complementary mitochondrial protective activity, supporting their development as scalable cell-free biotherapeutic platforms for neurodegenerative disorders.

bioengineering↗

bioRxiv2025

Platelet concentrate-derived extracellular vesicles promote adult hippocampal neurogenesis

Platelet-derived materials are emerging as promising, cell-free biotherapies for regenerative medicine. While platelet lysates have shown neuroprotective activity in preclinical models, the neurogenic potential of platelet concentrate-derived extracellular vesicles (pEVs) remains underexplored. Here, we evaluated the effects of human pEVs and a neuroprotective heat-treated human platelet lysate (HPPL) on adult hippocampal neurogenesis using both an ex vivo neurosphere assay and an in vivo intranasal administration model. pEVs selectively enhanced dentate gyrus (DG)-derived neurosphere growth, even in the absence of exogenous growth factors, and were internalized by neural precursors. In vivo, short-term pEV delivery increased EdU proliferating cells in the DG, while long-term administration (28 days) elevated the proportion of newborn mature neurons. By contrast, HPPL primarily promoted early neurogenesis by expanding immature DCX neurons. Quantitative proteomics of DG tissue after pEV treatment revealed 111 differentially expressed proteins, with enrichment in pathways related to oxidative phosphorylation, Notch4 signaling, myelination, and MHC class I-mediated antigen presentation. Downregulated proteins included cytoskeletal and translation-related regulators, suggesting a shift toward neuronal differentiation and circuit integration. Biophysical characterization confirmed the purity and vesicular nature of pEVs, with a defined protein cargo including immune modulators and ECM-interacting molecules such as CD44, lymphatic vessel endothelial hyaluronan receptor 1 (LYVE1), and complement proteins. These findings identify allogeneic pEVs as multifunctional agents that modulate neural precursor cell fate and brain tissue remodeling through coordinated metabolic and immunoregulatory mechanisms. This work supports the translational potential of pEV-based therapeutics for promoting hippocampal neurogenesis and cognitive repair in neurodegenerative and age-related brain disorders.

neuroscience↗

bioRxiv2024

Innovative platelet-derived extracellular vesicle drug delivery system for the treatment of corneal neovascularization

Platelet-derived extracellular vesicles (PEVs) have drawn attention due to their multifunctionality, ease of procurement, and abundant supply from clinical-grade platelet concentrates. PEVs can be easily endocytosed owing to their lipid bilayer membrane and nanosized structure, thereby increasing the bioavailability and functionality of their therapeutic effects. PEVs also possess multiple trophic factors that make them effective therapeutic agents. Since nanomedicine offers advantages over traditional therapies for eye diseases by overcoming physical ocular barriers, PEVs combined with an anti-angiogenic agent, kaempferol (KM), were evaluated for their ability to inhibit abnormal vessel formation in the cornea. Characterization of the nanoparticles indicated successful preparation of KM- loaded PEVs (PEV-KM) with a mean diameter of [~]160 nm and an encapsulation efficiency of [~]61%. PEV-KM was efficiently internalized into human vascular endothelial cells, resulting in inhibited function, evidenced by lower wound closure rates, reduced tube formation capacity, and downregulation of angiogenesis-related gene expression. Moreover, prolonged ocular retention was observed followed by topical application of PEV and PEV-KM in mouse eyes. In an alkali-burned corneal neovascularization (CoNV) mouse model, PEV (1%) was found to reduce vessel formation in the injured cornea. PEV with KM (1% PEV with KM 6 {micro}g/mL) showed an even stronger effect in suppressing CoNV and reducing the expression of proangiogenic and inflammatory cytokines. Together, our data suggests that topical administration of PEVs or in combination with KM (PEV-KM) is a promising therapeutic for managing CoNV.

bioengineering↗