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Modulation of epileptogenesis through transplantation of human mesenchymal stem cells with or without GDNF release

Waloschková, Eliška ; Melin, Esbjörn LU orcid ; Baumlin, Camille ; Andersson, My LU orcid ; Serrano, Alberto Martínez ; Kokaia, Merab LU and Ledri, Marco LU (2025) In Cellular and Molecular Life Sciences 82. p.1-17
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... (More)

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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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Epilepsy, Epileptogenesis, GDNF, Human mesenchymal stem cells, Inflammation
in
Cellular and Molecular Life Sciences
volume
82
article number
316
pages
1 - 17
publisher
Birkhäuser
external identifiers
  • scopus:105013808421
  • pmid:40839114
ISSN
1420-682X
DOI
10.1007/s00018-025-05853-z
language
English
LU publication?
yes
additional info
Publisher Copyright: © The Author(s) 2025.
id
bd583ee5-b6ea-419a-8724-53d5f063726b
date added to LUP
2026-09-24 10:45:54
date last changed
2026-09-25 03:00:02
@article{bd583ee5-b6ea-419a-8724-53d5f063726b,
  abstract     = {{<p>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.</p>}},
  author       = {{Waloschková, Eliška and Melin, Esbjörn and Baumlin, Camille and Andersson, My and Serrano, Alberto Martínez and Kokaia, Merab and Ledri, Marco}},
  issn         = {{1420-682X}},
  keywords     = {{Epilepsy; Epileptogenesis; GDNF; Human mesenchymal stem cells; Inflammation}},
  language     = {{eng}},
  pages        = {{1--17}},
  publisher    = {{Birkhäuser}},
  series       = {{Cellular and Molecular Life Sciences}},
  title        = {{Modulation of epileptogenesis through transplantation of human mesenchymal stem cells with or without GDNF release}},
  url          = {{http://dx.doi.org/10.1007/s00018-025-05853-z}},
  doi          = {{10.1007/s00018-025-05853-z}},
  volume       = {{82}},
  year         = {{2025}},
}