Multipronged Attack of Stem Cell Therapy in Treating the Neurological and Neuropsychiatric Symptoms of Epilepsy

Abstract

Epilepsy stands as a life-threatening disease that is characterized by unprovoked seizures. However, an important characteristic of epilepsy that needs to be examined is the neuropsychiatric aspect. Epileptic patients endure aggression, depression, and other psychiatric illnesses. Therapies for epilepsy can be divided into two categories: antiepileptic medications and surgical resection. Antiepileptic drugs are used to attenuate heightened neuronal firing and to lessen seizure frequency. Alternatively, surgery can also be conducted to physically cut out the area of the brain that is assumed to be the root cause for the anomalous firing that triggers seizures. While both treatments serve as viable approaches that aim to regulate seizures and ameliorate the neurological detriments spurred by epilepsy, they do not serve to directly counteract epilepsy’s neuropsychiatric traits. To address this concern, a potential new treatment involves the use of stem cells. Stem cell therapy has been employed in experimental models of neurological maladies, such as Parkinson’s disease, and neuropsychiatric illnesses like depression. Cell-based treatments for epilepsy utilizing stem cells such as neural stem cells (NSCs), mesenchymal stem cells (MSCs), and interneuron grafts have been explored in preclinical and clinical settings, highlighting both the acute and chronic stages of epilepsy. However, it is difficult to create an animal model to capitalize on all the components of epilepsy due to the challenges in delineating the neuropsychiatric aspect. Therefore, further preclinical investigation into the safety and efficacy of stem cell therapy in addressing both the neurological and the neuropsychiatric components of epilepsy is warranted in order to optimize cell dosage, delivery, and timing of cell transplantation.

Stem Cell Therapy in Treating Epilepsy

“…The utility of in vitro stem cell technology by patient-derived iPSCs to high-throughput screening of anti-seizure medications can be applied for personalized epilepsy therapy (Jiao et al, 2013 ; Kaufmann et al, 2015 ; Elitt et al, 2018 ; Lybrand et al, 2020 ). The potential major roles of stem cell therapy in epilepsy are seizure remission, inhibition of the progression of the epileptogenic process, prophylaxis against the development of chronic epilepsy, and improvement of cognitive function (Aligholi et al, 2021 ; Sadanandan et al, 2021 ; Ramos-Fresnedo et al, 2022 ). A phase I clinical trial study showed a favorable seizure reduction, a good safety profile, and improvement of pathological hallmarks in epilepsy patients treated with autologous MSCs (Hlebokazov et al, 2017 ).…”

The Endocannabinoid System in Glial Cells and Their Profitable Interactions to Treat Epilepsy: Evidence from Animal Models

“…In the last decade, different approaches have attempted to prevent seizures and to control them. These treatments, some obtained from pre-clinical studies, ranging from pharmacological therapies based on new compounds such as resveratrol or vitamin E [22,23]; cell therapies rooted on stem cells, interneuron precursor transplants [24][25][26] or reprograming reactive glia into interneurons [27], and gene therapies such as neuropeptide Y transfection [28,29] to clinical studies in humans, such as modern surgery with laser-induced thermal therapy (LITT); magnetic resonance-guided LITT (MRgLITT) [30,31]; brain stimulation [32,33], or even controlling seizures with diet such as a ketogenic diet or other regimens [34]. Since most AEDs available in the market are only preventing and treating the symptoms instead of acting on the molecular mechanisms, they produce numerous negative side effects that limit their therapeutic use [35][36][37].…”

Delivery of Stem Cell Secretome for Therapeutic Applications

“…Stem cells are defined as a group of cells with unlimited proliferation, self-renewing, and multilineage differentiation potential. , Novel therapies using stem cells have been evidenced with premium therapeutic efficacy in the treatment of diverse devastating diseases such as epilepsy, neonatal hypoxic-ischemic encephalopathy, autoimmune disease, and diabetic kidney disease. − However, one of the critical issues is the poor survival rate and potential tumorigenesis of stem cells after implantation in vivo . ,, Compared with pluripotent stem cells, such as induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs), mesenchymal stem/stromal cells (MSCs) lack tumorigenicity, have lower immunogenicity, and will not raise ethical concerns . Recent studies showed that paracrine effects of stem cells might predominate over cell differentiation during tissue repair. , The paracrine effects include anti-inflammation, antiapoptosis, host cell recruitment, enhanced cell proliferation, and proangiogenesis. − Compared to living cells, the secreted bioactive molecules, namely stem cell secretome, have various advantages such as easy preparation and storage, which are essential for their clinical applications. − …”