If You Just Add the Right Cells, You Could Prevent Seizures

Modulation of Epileptogenesis Through Transplantation of Human Mesenchymal Stem Cells With or Without GDNF Release Waloschková E, Melin E, Baumlin C, Andersson M, Serrano AM, Kokaia M, Ledri M. Modulation of epileptogenesis through transplantation of human mesenchymal stem cells with or without GDNF release. Cell Mol Life Sci. 2025 Aug 21;82(1):316. doi: 10.1007/s00018-025-05853-z. PMID: 40839114; PMCID: PMC12370614. Epilepsy is a central nervous system disorder causing uncontrollable seizures. One-third of patients do not respond to current medications, necessitating new treatments. This study targeted epileptogenesis, the process leading to chronic epilepsy, using human mesenchymal stem cells (MSCs) in a rodent model. MSC transplantation can positively affect neurodegenerative diseases by modifying inflammation. Additionally, glial cell line-derived neurotrophic factor (GDNF) may counteract seizures and tissue damage. We transplanted naïve immortalized human adipose-derived MSCs (Ctrl-MSCs) or GDNF-releasing MSCs (GDNF-MSCs, releasing 588.67 ± 20.14 pg/ml/24 h GDNF) into rat hippocampi after kainic acid-induced status epilepticus. Seizure progression was monitored for 5 weeks using video-EEG, behavioral assessments, and histological analysis. Both cell types influenced epileptogenesis. GDNF-MSCs delayed early-stage seizures, while Ctrl-MSCs reduced seizure frequency in later stages. Differences emerged in seizure development and cumulative seizure count, with Ctrl-MSCs showing significant seizure-attenuating effects. Behavioral differences were also noted: Ctrl-MSCs improved short-term memory and reduced anxiety, whereas GDNF-MSCs primarily reduced anxiety without significantly improving memory. This study highlights the therapeutic potential of MSCs, with or without GDNF, in modulating epileptogenesis, offering promising avenues for future clinical treatments.