Extracellular vesicles of human glial cells exert neuroprotective effects via brain miRNA modulation in a rat model of traumatic brain injury

• Published in: Scientific reports Vol. 13; no. 1; pp. 20388 - 18
• Main Authors: Salikhova, Diana I., Timofeeva, Angelika V., Golovicheva, Victoria V., Fatkhudinov, Timur Kh, Shevtsova, Yulia A., Soboleva, Anna G., Fedorov, Ivan S., Goryunov, Kirill V., Dyakonov, Alexander S., Mokrousova, Victoria O., Shedenkova, Margarita O., Elchaninov, Andrey V., Makhnach, Oleg V., Kutsev, Sergey I., Chekhonin, Vladimir P., Silachev, Denis N., Goldshtein, Dmitry V.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 21.11.2023; Nature Publishing Group; Nature Portfolio
• Subjects: 631/378/1687; 631/532; Animal models; Animals; Apoptosis; Astrocytes; Brain - metabolism; Brain Injuries, Traumatic - drug therapy; Brain Injuries, Traumatic - therapy; Extracellular vesicles; Extracellular Vesicles - metabolism; Glial cells; Glial stem cells; Graft rejection; Humanities and Social Sciences; Humans; Induced Pluripotent Stem Cells - metabolism; Intranasal administration; MicroRNAs; MicroRNAs - metabolism; miRNA; multidisciplinary; Neuroglia - metabolism; Neurological diseases; Neuronal-glial interactions; Neuroplasticity; Neuroprotection; Neuroprotective Agents - therapeutic use; NF-kappa B - metabolism; NF-κB protein; Paracrine signalling; Pluripotency; Progenitor cells; R&D; Rats; Rats, Wistar; Research & development; Science; Science (multidisciplinary); Sensorimotor system; Stem cells; Tau protein; Transcriptomes; Traumatic brain injury
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-023-47627-2

Stem cell-based therapeutic approaches for neurological disorders are widely studied. Paracrine factors secreted by stem cells in vitro and delivered intranasally might allow bypassing the disadvantages associated with a surgical cell delivery procedure with likely immune rejection of a transplant. In this study, we investigated the therapeutic effect of the extracellular vesicles secreted by glial progenitor cells (GPC-EV) derived from human induced pluripotent stem cell in a traumatic brain injury model. Intranasal administration of GPC-EV to Wistar rats for 6 days improved sensorimotor functions assessed over a 14-day observation period. Beside, deep sequencing of microRNA transcriptome of GPC-EV was estimate, and was revealed 203 microRNA species that might be implicated in prevention of various brain pathologies. Modulation of microRNA pools might contribute to the observed decrease in the number of astrocytes that inhibit neurorecovery processes while enhancing neuroplasticity by decreasing phosphorylated Tau forms, preventing inflammation and apoptosis associated with secondary damage to brain tissue. The course of GPC-EV administration was promoted the increasing protein levels of NF-κB in studied areas of the rat brain, indicating NF-κB dependent mechanisms as a plausible route of neuroprotection within the damaged area. This investigation showed that GPC-EV may be representing a therapeutic approach in traumatic brain injury, though its translation into the clinic would require an additional research and development.