TY - JOUR
T1 - Mesenchymal stem cell therapy for focal epilepsy
T2 - A systematic review of preclinical models and clinical studies
AU - Ramos-Fresnedo, Andres
AU - Perez-Vega, Carlos
AU - Domingo, Ricardo A.
AU - Lee, Seung Jin
AU - Perkerson, Ralph B.
AU - Zubair, Abba C.
AU - Takahisa, Kanekiyo
AU - Tatum, William
AU - Quinones-Hinojosa, Alfredo
AU - Middlebrooks, Erik H.
AU - Grewal, Sanjeet S.
N1 - Funding Information:
AQH was supported by the Mayo Clinic Professorship and a Clinician Investigator award, a Florida State Department of Health Research Grant, and the Mayo Clinic Graduate School, as well as the National Institutes of Health (NIH) (R43CA221490, R01CA200399, R01CA195503, and R01CA216855). EHM receives unrelated research support from Boston Scientific Corp. and Varian Medical Systems, Inc.
Publisher Copyright:
© 2022 International League Against Epilepsy.
PY - 2022/7
Y1 - 2022/7
N2 - 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 γ-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.
AB - 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 γ-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.
KW - animal model
KW - biologics
KW - clinical trial
KW - human study
KW - mesenchymal stem cells
UR - http://www.scopus.com/inward/record.url?scp=85129969019&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85129969019&partnerID=8YFLogxK
U2 - 10.1111/epi.17266
DO - 10.1111/epi.17266
M3 - Review article
C2 - 35451066
AN - SCOPUS:85129969019
SN - 0013-9580
VL - 63
SP - 1607
EP - 1618
JO - Epilepsia
JF - Epilepsia
IS - 7
ER -