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Mesenchymal stem cell therapy for focal epilepsy: A systematic review of preclinical models and clinical studies

Journal

EPILEPSIA
Volume 63, Issue 7, Pages 1607-1618

Publisher

WILEY
DOI: 10.1111/epi.17266

Keywords

animal model; biologics; clinical trial; human study; mesenchymal stem cells

Funding

  1. Florida State Department of Health Research
  2. Mayo Clinic Graduate School
  3. NIH [R43CA221490, R01CA200399, R01CA195503, R01CA216855]
  4. Boston Scientific Corp.
  5. Varian Medical Systems, Inc

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By systematically reviewing preclinical and clinical studies of MSCs for drug-resistant epilepsy, it was found that this therapy is safe and effective in reducing seizure burden, improving electrophysiological biomarkers, and alleviating comorbidities in patients. Further research is warranted to explore the full therapeutic potential of MSC therapy.
Drug-resistant epilepsy (DRE) is characterized by recurrent seizures despite appropriate treatment with antiseizure medication (ASM). Due to their regenerative and immunomodulatory potential, therapies with biologics such as mesenchymal stem cells (MSCs) offer a potential therapeutic benefit for structural causes of epilepsy, such as hippocampal sclerosis. In this article, we report a systematic review of the literature evaluating the preclinical and clinical studies of MSCs for DRE. Medline, Ovid EMBASE, Scopus, and the Cochrane Databases were searched electronically from their dates of inception to November 2021 using the following keywords: ((mesenchymal) AND (stem cell)) AND ((epilepsy) OR (convulsion) OR (seizures)). This review followed Preferred Reporting Items for Systemic Reviews and Meta-Analyses (PRISMA) guidelines. The initial query identified 488 studies representing 323 unique manuscripts. After application of selection criteria, 15 studies were included in this systematic review; 11 were preclinical studies and 4 were clinical studies. All preclinical studies were performed in rodents and all clinical studies were phase 1 trials. Thus far, therapy with MSCs appears to be safe for use in humans, as no severe adverse events related directly to the therapy were reported. Furthermore, MSC therapy appears to provide a statistically significant clinical benefit by reducing the seizure burden of patients, reducing the electrophysiological biomarkers of epilepsy, and improving their comorbidities, such as depression and anxiety. In addition, animal studies reveal that the therapy exerts its effect by reducing aberrant mossy fiber sprouting (reduce excitatory pathways) and increasing gamma-aminobutyric acid (GABA)ergic interneurons (increase inhibitory pathways). Both preclinical and clinical studies have shown MSC therapy to be safe and preliminary effective, thus warranting further studies to investigate its therapeutic potential.

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