Basic Science and Pathogenesis

Area of Science:

• Neuroscience
• Immunology
• Regenerative Medicine

Background:

• Ischemic stroke (IS) is a known risk factor for Alzheimer's disease (AD).
• Microglial reactivity is implicated in both IS and AD, presenting a therapeutic target.
• Previous work indicated mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) modulate microglial reactivity in IS models.

Purpose of the Study:

• To investigate if MSC-EVs' effects on microglia differ between early and late phases of IS.
• To assess the impact of MSC-EVs on pro-inflammatory and anti-inflammatory microglial markers in IS models.

Main Methods:

• A systematic meta-analysis was conducted following PRISMA 2020 guidelines, with the protocol registered on PROSPERO.
• Searched EMBASE, PubMed, and Web of Science for studies on MSC-EVs treatment in IS animal models.
• Subgroup analyses compared MSC-EV effects in early (48-72h) and late (≥168h) IS phases using random-effects models.

Main Results:

• MSC-EVs significantly reduced pro-inflammatory markers (Iba1+, CD16+, CD32+, iNOS+) in both early and late IS phases.
• MSC-EVs significantly increased anti-inflammatory markers (Iba1+, Arg-1+, CD206+) in both early and late IS phases.
• These effects were consistent across different disease phases, indicating persistent modulation.

Conclusions:

• MSC-EVs demonstrate consistent efficacy in decreasing pro-inflammatory and increasing anti-inflammatory microglial responses in IS models.
• The modulatory effects of MSC-EVs on microglia are phase-independent in IS.
• These findings support MSC-EVs as a potential therapeutic strategy for IS recovery and potentially for AD.