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November 1, 2024Journal of Extracellular VesiclesOpen Access

Extracellular vesicles from human‐induced pluripotent stem cell‐derived neural stem cells alleviate proinflammatory cascades within disease‐associated microglia in Alzheimer's disease

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To determine whether intranasal administration of extracellular vesicles derived from human induced pluripotent stem cell-derived neural stem cells can suppress neuroinflammatory cascades and slow Alzheimer's disease progression.
Administered hiPSC-NSC-EVs intranasally to 3-month-old 5xFAD Alzheimer's model mice and applied them in vitro to cultured human microglia challenged with amyloid-beta oligomers.
Conducted single-cell RNA sequencing to profile transcriptomic shifts in microglia and astrocytes, and evaluated neuroinflammation, hippocampal plaque and p-tau burden, microglial phagocytosis, and behavioral outcomes 2 months post-treatment.
hiPSC-NSC-EVs integrated into plaque-associated microglia and astrocytes, downregulating genes linked to disease-associated microglia, NLRP3 inflammasome activation, and interferon-1 signaling.
Treatment produced sustained reductions in microglial clusters, inflammasome complexes, astrocyte hypertrophy, amyloid-beta plaques, and phosphorylated tau in the hippocampus without inhibiting microglial phagocytosis.
EV-treated mice displayed significant improvements in cognitive performance and mood-related behaviors compared to untreated disease models.

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Implication

Preclinical study shows intranasal stem cell vesicles curb neuroinflammation and amyloid burden in Alzheimer's mice, indicating therapeutic potential as a disease-modifying biologic.

Cite This Study

Madhu et al. (2024) studied this question.

synapsesocial.com/papers/69dd543080eea7d3f699b769 https://doi.org/10.1002/jev2.12519

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Implication

Preclinical study shows intranasal stem cell vesicles curb neuroinflammation and amyloid burden in Alzheimer's mice, indicating therapeutic potential as a disease-modifying biologic.

Extracellular vesicles from human‐induced pluripotent stem cell‐derived neural stem cells alleviate proinflammatory cascades within disease‐associated microglia in Alzheimer's disease

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Discussion

Implication

Cite This Study

Extracellular vesicles from human‐induced pluripotent stem cell‐derived neural stem cells alleviate proinflammatory cascades within disease‐associated microglia in Alzheimer's disease

Key Points

Discussion

Implication

Cite This Study

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