Microglia morphological response to mesenchymal stromal cell extracellular vesicles demonstrates EV therapeutic potential for modulating neuroinflammation DOI Creative Commons

Kanupriya R. Daga,

Andrew M. Larey,

Maria G. Morfin

et al.

Journal of Biological Engineering, Journal Year: 2024, Volume and Issue: 18(1)

Published: Oct. 17, 2024

Mesenchymal stromal cell derived extracellular vesicles (MSC-EVs) are a promising therapeutic for neuroinflammation. MSC-EVs can interact with microglia, the resident immune cells of brain, to exert their immunomodulatory effects. In response inflammatory cues, such as cytokines, microglia undergo phenotypic changes indicative function e.g. morphology and secretion. However, these in not well understood. Additionally, no disease-relevant screening tools assess MSC-EV bioactivity exist, which has further impeded clinical translation. Here, we developed quantitative, high throughput morphological profiling approach neuroinflammation- relevant signals whether this be used indicate MSC-EVs.

Language: Английский

Neurotropic murine coronavirus mediated demyelination: Factors dampening pathogenesis DOI
Mi‐Hyun Hwang, Cornelia C. Bergmann

Journal of Neuroimmunology, Journal Year: 2024, Volume and Issue: 393, P. 578382 - 578382

Published: June 1, 2024

Language: Английский

Citations

1
Bithiazole inhibitors of PI4KB show broad-spectrum antiviral activity against different viral families. DOI Creative Commons
Maria Grazia Martina,

Vincent Carlen,

Sarah Van der Reysen

et al.

Antiviral Research, Journal Year: 2024, Volume and Issue: 231, P. 106003 - 106003

Published: Sept. 10, 2024

Language: Английский

Citations

1
Lipopolysaccharide Enhances Microglia Antiviral Control of Betacoronavirus Infection through TLR4-Dependent Induction of IFNβ with Concomitant Modulation of dsRNA Sensors MDA5 and TLR3 DOI Creative Commons

Elijah Davis,

Adam M. Glass,

Brett Arthur LaBier

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: May 30, 2024

Abstract Microglia play a pivotal role in brain homeostasis and are essential to protective immunity within the central nervous system by coordinating innate immune response neuroinvasive pathogens. Bacterial endotoxin (lipopolysaccharide, LPS) is most used pro-inflammatory stimulus for microglia, both in vitroand vivo. However, impact of LPS microglia viral infection, including coronaviruses remains ill-defined. Murine productively infect well established models RNA virus-induced encephalitis demyelination. In present study, we investigated effects TLR4 stimulation with TLR4-specific agonist [smooth (s)-form (E. coli 0111:B4)] on murine coronavirus MHV-JHM -A59 infection vitro. Mechanistically, our data revealed that restrict replication through TLR4-dependent induction interferon (IFN-b) concomitant modulation dsRNA sensors melanoma differentiation-associated gene 5 (MDA5) toll-like receptor 3 (TLR3). Moreover, absence induces upregulation MDA5 expression activation TLR3, as measured phosphorylation its residue Y759, hallmark TLR3 signaling initiation. Supporting LPS-induced activation, demonstrated selectively contributes TLR4-dependent, neuroinflammation even virus infection. Overall, study provides novel mechanistic insights regarding responses highlights previously unrecognized crosstalk between bacterial implications beyond

Language: Английский

Citations

0
Microglia Morphological Response to Mesenchymal Stromal Cell Extracellular Vesicles Demonstrates EV Therapeutic Potential for Modulating Neuroinflammation DOI

Kanupriya R. Daga,

Andrew M. Larey,

Maria G. Morfin

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 3, 2024

ABSTRACT Background Mesenchymal stromal cell derived extracellular vesicles (MSC-EVs) are a promising therapeutic for neuroinflammation. MSC-EVs can interact with microglia, the resident immune cells of brain, to exert their immunomodulatory effects. In response inflammatory cues, such as cytokines, microglia undergo phenotypic changes indicative function e.g. morphology and secretion. However, these in not well understood. Additionally, no disease-relevant screening tools assess MSC-EV bioactivity exist, which has further impeded clinical translation. Here, we developed quantitative, high throughput morphological profiling approach neuroinflammation-relevant signals whether this be used indicate MSC-EVs. Results Using an immortalized human cell-line, observed increased size (perimeter, major axis length) complexity (form factor) upon stimulation interferon-gamma (IFN-γ) tumor necrosis factor-alpha (TNF-α). Upon treatment MSC-EVs, overall score (determined using principal component analysis) shifted towards unstimulated morphology, indicating that bioactive modulate microglia. The effects TNF-γ/IFN-α stimulated were concomitant reduced secretion 14 chemokines/cytokines (e.g. CXCL6, CXCL9) 12 CXCL8, CXCL10). Proteomic analysis lysates revealed significant increases 192 proteins HIBADH, MEAK7, LAMC1) decreases 257 PTEN, TOM1, MFF) treatment. Of note, many involved regulation migration. Gene Set Variation Analysis upregulation pathways associated response, cytokine production, infiltration T cells, NK cells) Semaphorin, RHO/Rac signaling). mitochondrial measured suggesting metabolism. Conclusion This study comprehensively demonstrates on microglial secretion, cellular proteome, content. Our high-throughput, rapid, low-cost enables batches manufacturing conditions enhance EV mitigate functional heterogeneity disease relevant manner. is highly generalizable adapted refined based selection signal, target cell, product.

Language: Английский

Citations

0
Microglia morphological response to mesenchymal stromal cell extracellular vesicles demonstrates EV therapeutic potential for modulating neuroinflammation DOI Creative Commons

Kanupriya R. Daga,

Andrew M. Larey,

Maria G. Morfin

et al.

Journal of Biological Engineering, Journal Year: 2024, Volume and Issue: 18(1)

Published: Oct. 17, 2024

Mesenchymal stromal cell derived extracellular vesicles (MSC-EVs) are a promising therapeutic for neuroinflammation. MSC-EVs can interact with microglia, the resident immune cells of brain, to exert their immunomodulatory effects. In response inflammatory cues, such as cytokines, microglia undergo phenotypic changes indicative function e.g. morphology and secretion. However, these in not well understood. Additionally, no disease-relevant screening tools assess MSC-EV bioactivity exist, which has further impeded clinical translation. Here, we developed quantitative, high throughput morphological profiling approach neuroinflammation- relevant signals whether this be used indicate MSC-EVs.

Language: Английский

Citations

0