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Basic Science and Pathogenesis.

Luis Pedro Bernardi1, Thomas Hugentobler Schlickmann1, Giovanna Carello-Collar2

  • 1Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.

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Summary
This summary is machine-generated.

Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) consistently modulate microglial responses in animal models of ischemic stroke (IS), reducing inflammation and promoting anti-inflammatory effects. These findings suggest MSC-EVs may aid recovery in IS and Alzheimer's disease (AD).

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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.