Effects of Human Umbilical Cord Mesenchymal Stem Cell-Derived Exosomes on an Ischemic Stroke Rat Model
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Abstract
Introduction: Ischemic stroke remains a leading cause of disability worldwide, with limited therapeutic options beyond the acute stage. Mesenchymal stem cell (MSC)-derived exosomes have emerged as a promising cell-free therapeutic strategy due to their immunomodulatory and neurotrophic properties. The current study aimed to evaluate the neuroprotective effects of human umbilical cord MSC-derived exosomes (hUC-MSC-Exos) on neurological function, infarct volume, and inflammatory response in a rat model of middle cerebral artery occlusion (MCAO).
Materials and methods: A total of 36 adult male rats weighing 250-300 grams and aged 8-10 weeks were randomly divided into three groups of 12 rats each. The first group underwent surgery without occlusion (Group A). The second group consisted of MCAO rats that received 100 µL of phosphate-buffered saline (PBS) intravenously (Group B). The third group consisted of MCAO rats that received 100 µg of hUC-MSC-Exos (1 × 10¹⁰ particles), diluted in 100 µL of sterile PBS, administered intravenously (Group C). Ischemic stroke was induced by 60-minute transient MCAO followed by reperfusion. Neurological deficits were assessed using the modified neurological severity score (mNSS) and grip strength test at 24 hours, 48 hours, and 7 days post-stroke. On day 7, brains were harvested for 2,3,5-triphenyltetrazolium chloride (TTC) staining to measure infarct volume, and cortical tissue was collected to measure tumor necrosis factor-alpha (TNF-α) and Interleukin-10 (IL-10) levels by enzyme-linked immunosorbent assay (ELISA).
Results: Administration of 100 μg of hUC-MSC-Exos significantly improved neurological function compared To Group B, as evidenced by reduced mNSS scores from 12.4 ± 1.2 to 11.8 ± 1.4 in 24 hours, from 11.2 ± 1.3 to 8.3 ± 1.1 in 48 hours, and from 9.6 ± 1.5 to 4.5 ± 0.9 on day 7, along with increased grip strength. Moreover, TTC staining revealed a significant reduction in infarct volume in Group C compared to the control group. The pro-inflammatory cytokine TNF-α and IL-10 in the ischemic cortical tissue in Group C were significantly decreased compared to Group B.
Conclusion: The systemic administration of hUC-MSC-Exos had neuroprotective effects on rats by reducing infarct size, improving motor function, and modulating the inflammatory response.
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