Modulation of epileptogenesis through transplantation of human mesenchymal stem cells with or without GDNF release
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 roden...
| Autores: | , , , , , , |
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| Tipo de documento: | artigo |
| Estado: | Versão publicada |
| Data de publicação: | 2025 |
| País: | España |
| Recursos: | Consejo Superior de Investigaciones Científicas (CSIC) |
| Repositório: | DIGITAL.CSIC. Repositorio Institucional del CSIC |
| OAI Identifier: | oai:digital.csic.es:10261/423703 |
| Acesso em linha: | http://hdl.handle.net/10261/423703 |
| Access Level: | Acceso aberto |
| Palavra-chave: | Human mesenchymal stem cells GDNF Epileptogenesis Epilepsy Inflammation |
| Resumo: | 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. |
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