Extracellular Vesicles Derived from Human Umbilical Cord Perivascular Cells Improve Functional Recovery in Brain Ischemic Rat via the Inhibition of Apoptosis

Abstract

Background: Ischemic stroke, as a health problem caused by the reduced blood supply to the brain, can lead to the neuronal death. The number of reliable therapies for stroke is limited. MSCs exhibit therapeutic achievement. A major limitation of MSC application in cell therapy is the short survival span. MSCs affect target tissues through the secretion of many paracrine agents including EVs. This study aimed to investigate the effect of HUCPVCs-derived EVs on apoptosis, functional recovery, and neuroprotection. Methods: Ischemia was induced by MCAO in male Wistar rats. Animals were classified into sham, MCAO, MCAO + HUCPVC, and MCAO + EV groups. Treatments began at two hours after ischemia. Expressions of apoptotic-related proteins (BAX/BCl-2 and caspase-3 and -9), the amount of TUNEL-positive cells, neuronal density (MAP2), and dead neurons (Nissl staining) were assessed on day seven post MCAO. Results: Administration of EVs improved the sensorimotor function ( p < 0.001) and reduced the apoptotic rate of Bax/Bcl-2 ratio ( p < 0.001), as well as caspases and TUNEL-positive cells ( p < 0.001) in comparison to the MCAO group. EV treatment also reduced the number of dead neurons and increased the number of MAP2 + cells in the IBZ ( p < 0.001), as compared to the MCAO group. Conclusion: Our findings showed that HUCPVCs-derived EVs are more effective than their mother’s cells in improving neural function, possibly via the regulation of apoptosis in the ischemic rats. The strategy of cell-free extracts is, thus, helpful in removing the predicaments surrounding cell therapy in targeting brain diseases.

Mesenchymal Stem Cell-Derived Exosomes as New Remedy for the Treatment of Neurocognitive Disorders

“…By providing trophic, vasoactive, and immunomodulatory factors in injured neurons and microglia, MSC-Exos inhibit detrimental immune response and promote neurogenesis and neuritogenesis [ 35 ]. Accordingly, several lines of evidence demonstrated that MSC-Exos efficiently improved cognition, learning deficiency, and memory loss in damaged and ischemic hippocampal neurons [ 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 ].…”

“…Yang and colleagues showed that MSC-Exos improved postoperative cognitive dysfunction, a severe complication of cardiopulmonary bypass, by reducing hippocampal neuronal apoptosis [ 42 ]. MSC-Exo-dependent prevention of apoptosis was also responsible for improved cognitive function of rats suffering from ischemic brain injury [ 43 ]. MSC-Exos down-regulated expression of pro-apoptotic molecules (Bax, caspase-3 and -9) and enhanced expression of anti-apoptotic Bcl-2 protein, which significantly reduced the total number of dead neurons and increased neuronal density in the ischemic boundary zone [ 43 ].…”

Effects of extracellular vesicles for ischemic stroke: A meta‑analysis of preclinical studies

“…There were 20 studies were included in the meta-analysis (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32). All articles were published between 2015 and 2023.…”

Contribution of Extracellular Vesicles and Molecular Chaperones in Age-Related Neurodegenerative Disorders of the CNS

“…Systemic injection of exosomes has been found to be effective in the transfer of small interfering RNA (siRNA) into the mice brain [ 79 ]. Given their implications in both physiological and pathological processes, it can be helpful to establish beneficial preventive plans and design successful therapeutic alternatives, either to mimic EVs or engineering them for a new purpose [ 27 , 80 ].…”