Extracellular vesicles MicroRNAs in stroke therapy: recent advances and translational potential

Area of Science:

• Neuroscience
• Biotechnology
• Regenerative Medicine

Background:

• Ischemic stroke, comprising ~87% of strokes, faces limitations with current reperfusion therapies due to narrow time windows.
• Small extracellular vesicles (sEVs) offer potential therapeutic benefits by crossing the blood-brain barrier to deliver microRNAs (miRNAs) that modulate key post-stroke processes.

Purpose of the Study:

• To critically review the pathogenesis of ischemic stroke.
• To evaluate preclinical advancements in small extracellular vesicle-microRNA (sEV-miRNA) therapy for stroke.
• To identify and discuss translational barriers impeding the clinical application of sEV-miRNA therapy.

Main Methods:

• Comprehensive literature review of preclinical studies on sEV-miRNA therapy in ischemic stroke models (e.g., MCAO).
• Analysis of current methodologies for sEV isolation and characterization, referencing MISEV2023 guidelines.
• Evaluation of miRNA cargo, biodistribution, and potential off-target effects of sEVs.

Main Results:

• Preclinical studies demonstrate sEV-miRNAs' potential to influence inflammation, apoptosis, angiogenesis, and neurogenesis post-stroke.
• Significant heterogeneity exists in miRNA cargo and challenges in standardizing sEV isolation protocols.
• Key translational hurdles include dosing uncertainties, limited biodistribution data, regulatory issues, and the absence of stroke-specific clinical trials.

Conclusions:

• sEV-miRNA therapy holds significant preclinical promise for ischemic stroke treatment.
• Standardization of sEV isolation, characterization, and rigorous clinical validation are crucial for therapeutic translation.
• Further research is needed to overcome identified barriers and develop precision stroke therapies utilizing sEV-miRNA.