ABSTRACT
Background and Aim: Epilepsy is a chronic neurological disorder characterized by recurrent seizures, neuronal degeneration, and cognitive impairment. Current antiepileptic therapies mainly control seizures and do not effectively prevent epileptogenesis or restore neurological function. Human umbilical cord mesenchymal stem cells (HuMSCs) and their cell-free derivatives, including secretome and exosomes, have emerged as promising regenerative therapies. This study aimed to compare the neuroprotective and cognitive effects of HuMSCs, secretome, and exosomes in a rat model of pilocarpine-induced epilepsy.
Materials and Methods: Thirty male Wistar rats were randomly allocated into five groups (n = 6/group): healthy control, untreated epilepsy, HuMSC-treated epilepsy, secretome-treated epilepsy, and exosome-treated epilepsy. Epilepsy was induced by intraperitoneal pilocarpine administration following scopolamine pre-treatment. Treatments were administered intravenously on days 14, 28, and 42 after induction. Cognitive performance was assessed using the Morris Water Maze test between days 50 and 56. Histopathological examination of the hippocampus, immunohistochemical evaluation, and quantitative polymerase chain reaction analysis of synaptic vesicle glycoprotein 2A (SV2A) and SRY-box transcription factor 10 (SOX10) expression were performed to determine therapeutic efficacy.
Results: HuMSC therapy significantly reduced hippocampal neuronal damage compared with untreated epilepsy, secretome, and exosome groups (p < 0.05). The mean number of damaged neurons was lowest in the HuMSC-treated group and approached normal control values. HuMSC treatment restored SV2A and SOX10 expression to levels comparable with those of healthy controls, indicating improved synaptic integrity and glial support. In contrast, secretome treatment produced moderate improvement, whereas exosome treatment showed limited therapeutic benefit. Cognitive assessment revealed significantly shorter escape latency and superior spatial learning performance in the HuMSC-treated rats compared with all other epilepsy groups (p < 0.05). Behavioral improvements were consistent with the molecular and histopathological findings, demonstrating enhanced neuroprotection and functional recovery following HuMSC administration.
Conclusion: HuMSC therapy provided superior neuroprotective, molecular, and cognitive benefits compared with secretome and exosome treatments in a pilocarpine-induced epilepsy model. These findings support the potential of HuMSCs as a regenerative therapeutic strategy for epilepsy and suggest that intact stem cells may offer greater therapeutic efficacy than their cell-free derivatives. Further studies are required to optimize treatment protocols and evaluate long-term translational potential.
Keywords: cognitive function, epilepsy, exosomes, human umbilical cord mesenchymal stem cells, neuroprotection, secretome, spatial learning, stem cell therapy.