Modulation of epileptogenesis through transplantation of human mesenchymal stem cells with or without GDNF release
Abstract 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) i...
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2025-08-01
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| Series: | Cellular and Molecular Life Sciences |
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| Online Access: | https://doi.org/10.1007/s00018-025-05853-z |
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| author | Eliška Waloschková Esbjörn Melin Camille Baumlin My Andersson Alberto Martínez Serrano Merab Kokaia Marco Ledri |
| author_facet | Eliška Waloschková Esbjörn Melin Camille Baumlin My Andersson Alberto Martínez Serrano Merab Kokaia Marco Ledri |
| author_sort | Eliška Waloschková |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-ec24295629d240fd9f3f6e483cccd7c3 |
| institution | Kabale University |
| issn | 1420-9071 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Springer |
| record_format | Article |
| series | Cellular and Molecular Life Sciences |
| spelling | doaj-art-ec24295629d240fd9f3f6e483cccd7c32025-08-24T11:12:36ZengSpringerCellular and Molecular Life Sciences1420-90712025-08-0182111710.1007/s00018-025-05853-zModulation of epileptogenesis through transplantation of human mesenchymal stem cells with or without GDNF releaseEliška Waloschková0Esbjörn Melin1Camille Baumlin2My Andersson3Alberto Martínez Serrano4Merab Kokaia5Marco Ledri6Experimental Epilepsy Group, Epilepsy Center, Department of Clinical Sciences, Lund University HospitalExperimental Epilepsy Group, Epilepsy Center, Department of Clinical Sciences, Lund University HospitalDepartment of Molecular Biology, Department of Molecular Neuropathology, Center of Molecular Biology Severo Ochoa (UAM-CSIC), Universidad Autónoma de MadridCellular Neurophysiology and Epilepsy Group, Epilepsy Center, Department of Clinical Sciences, Lund University HospitalDepartment of Molecular Biology, Department of Molecular Neuropathology, Center of Molecular Biology Severo Ochoa (UAM-CSIC), Universidad Autónoma de MadridExperimental Epilepsy Group, Epilepsy Center, Department of Clinical Sciences, Lund University HospitalMolecular Neurophysiology and Epilepsy Group, Epilepsy Center, Department of Clinical Sciences, Lund University HospitalAbstract 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.https://doi.org/10.1007/s00018-025-05853-zHuman mesenchymal stem cellsGDNFEpileptogenesisEpilepsyInflammation |
| spellingShingle | Eliška Waloschková Esbjörn Melin Camille Baumlin My Andersson Alberto Martínez Serrano Merab Kokaia Marco Ledri Modulation of epileptogenesis through transplantation of human mesenchymal stem cells with or without GDNF release Cellular and Molecular Life Sciences Human mesenchymal stem cells GDNF Epileptogenesis Epilepsy Inflammation |
| title | Modulation of epileptogenesis through transplantation of human mesenchymal stem cells with or without GDNF release |
| title_full | Modulation of epileptogenesis through transplantation of human mesenchymal stem cells with or without GDNF release |
| title_fullStr | Modulation of epileptogenesis through transplantation of human mesenchymal stem cells with or without GDNF release |
| title_full_unstemmed | Modulation of epileptogenesis through transplantation of human mesenchymal stem cells with or without GDNF release |
| title_short | Modulation of epileptogenesis through transplantation of human mesenchymal stem cells with or without GDNF release |
| title_sort | modulation of epileptogenesis through transplantation of human mesenchymal stem cells with or without gdnf release |
| topic | Human mesenchymal stem cells GDNF Epileptogenesis Epilepsy Inflammation |
| url | https://doi.org/10.1007/s00018-025-05853-z |
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