Effects of cell therapy on seizures in animal models of epilepsy: Systematic review and meta‐analysis

This study was undertaken to systematically evaluate the efficacy of cell therapy in reducing seizures in animal models of chronic epilepsy. Three databases, Ovid MEDLINE, Ovid Embase, and Web of Science, were searched using predetermined eligibility criteria. The relevant preclinical controlled studies were included for review and meta-analysis using a random-effects model to calculate summary estimates of the effect size (percentage reduction in seizures). The degree of heterogeneity among the included studies was assessed using the I² statistic. Subgroup meta-analysis and meta-regression were performed to further elucidate the sources of heterogeneity. Thirty published studies met the eligibility criteria, including a total of 1306 animals. The majority of studies used kainic acid and pilocarpine status epilepticus models of mesial temporal lobe epilepsy (MTLE). The random effects model revealed an overall reduction in seizure frequency of 54.8% (95% confidence interval = 48.0558-61.5455) compared to the control, and the heterogeneity was 87.1% among the included studies. The meta-regression revealed that seven study characteristics significantly accounted for the between-study heterogeneity. They can be grouped into three broad categories: epilepsy-specific, animal-specific, and cell transplantation-specific. The greatest seizure reduction was observed in the post-kainic acid status epilepticus model of chronic MTLE, when the cells were delivered intravenously and when the seizure reduction was measured as seizure frequency. Embryonic stem cell transplantation showed the greatest efficacy in reducing seizures. Cell transplantation shows favorable efficacy as a treatment that can reduce seizure recurrence in chronic animal models of epilepsy. High heterogeneity between studies reflects the diverse methodologies employed in preclinical research on cell therapy for epilepsy. Despite these encouraging findings, the high risk of publication bias and variability in study design emphasize the need for further robust preclinical studies to confirm these reported outcomes.