Study on the Therapeutic Effects and Mechanisms of Human Mesenchymal Stem Cell-Derived Exosomes Carrying NGF Gene in Treating Ischemic Stroke in Rats

Abstract

Objective: To investigate the therapeutic effects and mechanisms of human mesenchymal stem cell-derived exosomes (hMSCs-Exo) carrying the NGF gene in treating ischemic stroke in rats, aiming to provide new insights and treatment methods for ischemic stroke therapy. Methods: After successful construction of the cerebral ischemia model in 40 male SPF-grade SD rats aged 6–8 weeks, the model rats were randomly divided into 4 groups: Sham group, PBS group, hMSCs-Exo group, and NGF-hMSCs-Exo group, with 10 rats in each group. The rat MCAO model was prepared using the classic filament method, and NGF-hMSCs-Exo were injected via the tail vein into the MCAO model rats. The expression of the NGF gene in brain ischemic tissues, neuronal regeneration, and rat neurological function recovery were observed using TTC staining, memory function evaluation, Western blot, qRT-PCR, and other methods. Results: Compared with the Sham group, neurological deficits were significant in the PBS group (P < 0.01). Compared with the PBS group, neurological scores improved in the hMSCs-Exo group and NGF-hMSCs-Exo group (P < 0.05). Compared with the hMSCs-Exo group, the improvement in neurological deficits was more significant in the NGF-hMSCs-Exo group (P < 0.05). The infarct area after NGF-hMSCs-Exo intervention was significantly reduced (P < 0.05) compared with the Sham group. Compared with the PBS group, relative expression levels of NGF mRNA and protein decreased, while Caspase-3 mRNA and protein expression significantly increased in the PBS group (P < 0.01). Compared with the PBS group and hMSCs-Exo group, there were differences in NGF and Caspase-3 mRNA and protein expression in the NGF-hMSCs-Exo group rat brain tissues (P < 0.05). Conclusion: Treatment with human mesenchymal stem cell-derived exosomes carrying the NGF gene improves cognitive function and exerts protective effects on SD rats while inhibiting apoptotic levels in cells.