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Updated: Oct 19, 2025

Isolation and Flow Cytometric Assessment of Neuroimmune Interactions in a Mini-Stroke Murine Model
Published on: June 20, 2025
Modulating poststroke inflammatory mechanisms: Novel aspects of mesenchymal stem cells, extracellular vesicles and
Wen-Qiang Xin1, Wei Wei1, Yong-Li Pan1
1Department of Neurology, University Medical Center Göttingen, Göttingen 37075, Germany.
Abstract:
Inflammation plays an important role in the pathological process of ischemic stroke, and systemic inflammation affects patient prognosis. As resident immune cells in the brain, microglia are significantly involved in immune defense and tissue repair under various pathological conditions, including cerebral ischemia. Although the differentiation of M1 and M2 microglia is certainly oversimplified, changing the activation state of microglia appears to be an intriguing therapeutic strategy for cerebral ischemia. Recent evidence indicates that both mesenchymal stem cells (MSCs) and MSC-derived extracellular vesicles (EVs) regulate inflammation and modify tissue repair under preclinical stroke conditions. However, the precise mechanisms of these signaling pathways, especially in the context of the mutual interaction between MSCs or MSC-derived EVs and resident microglia, have not been sufficiently unveiled. Hence, this review summarizes the state-of-the-art knowledge on MSC- and MSC-EV-mediated regulation of microglial activity under ischemic stroke conditions with respect to various signaling pathways, including cytokines, neurotrophic factors, transcription factors, and microRNAs.
Insights
Mesenchymal stem cells (MSCs) and their extracellular vesicles (EVs) show promise in modulating microglial activity following ischemic stroke. This review explores the signaling pathways involved in MSC and MSC-EV interactions with microglia for potential therapeutic strategies.
Area of Science:
- Neuroscience
- Immunology
- Regenerative Medicine
Background:
- Inflammation is a key factor in ischemic stroke pathology, impacting patient outcomes.
- Microglia, the brain's resident immune cells, are crucial in immune defense and repair after cerebral ischemia.
- Modulating microglial activation states presents a potential therapeutic avenue for ischemic stroke.
Purpose of the Study:
- To review current knowledge on how mesenchymal stem cells (MSCs) and MSC-derived extracellular vesicles (EVs) regulate microglial activity in ischemic stroke.
- To elucidate the signaling pathways involved in the interaction between MSCs/MSC-EVs and microglia.
- To highlight potential therapeutic strategies for ischemic stroke based on MSC-microglia interactions.
Main Methods:
- Literature review of preclinical studies on MSCs, MSC-EVs, and microglial responses in ischemic stroke models.
- Analysis of signaling pathways, including cytokines, neurotrophic factors, transcription factors, and microRNAs.
- Synthesis of current understanding regarding MSC- and MSC-EV-mediated neuroinflammation and tissue repair.
Main Results:
- MSCs and MSC-EVs demonstrate immunomodulatory effects relevant to ischemic stroke.
- These cells and vesicles influence microglial polarization and function through various molecular signaling pathways.
- Evidence suggests a complex interplay between MSCs/MSC-EVs and microglia impacting stroke recovery.
Conclusions:
- MSCs and MSC-EVs offer a promising therapeutic approach for ischemic stroke by modulating microglial responses.
- Further research into the precise signaling mechanisms is needed to optimize MSC- and MSC-EV-based therapies.
- Targeting the MSC-microglia axis holds potential for improving outcomes in ischemic stroke patients.

