{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T05:14:35Z","timestamp":1766985275876,"version":"3.48.0"},"reference-count":149,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T00:00:00Z","timestamp":1766707200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science Center, Poland","award":["2018\/31\/B\/NZ3\/01879"],"award-info":[{"award-number":["2018\/31\/B\/NZ3\/01879"]}]},{"name":"Ministry of Education and Science","award":["N41\/DBS\/000606"],"award-info":[{"award-number":["N41\/DBS\/000606"]}]},{"name":"NOVO Nordisk Foundation, Denmark","award":["NNF23OC0081536"],"award-info":[{"award-number":["NNF23OC0081536"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Temporal lobe epilepsy (TLE), the most common form of epilepsy, is often resistant to symptomatic treatment and characterized by persistent neuroinflammation, creating an urgent need for therapeutic strategies that can modulate early disease mechanisms. In this study, we examined the ability of the human MSC-derived secretome to influence epileptic hippocampal tissue during the latent phase of epileptogenesis using an ex vivo model. For this purpose, we characterized the MSC-derived secretome using multiplex Luminex profiling, optimized organotypic hippocampal cultures (OHCs) by evaluating cell viability, validated the pilocarpine-induced TLE model both morphologically and electrophysiologically, and investigated the influence of MSC-conditioned medium (MSC-CM) on epileptic hippocampal tissue. Using mouse-derived OHCs, we found that MSC-CM supports the preservation of nestin- and doublecortin (DCX)-positive progenitor cells, reduces NF-\u03baB (p50\/p105) levels, decreases LDH release into the culture medium, and modulates IL-6 secretion during the latent phase of epileptogenesis. Taken together, these findings suggest that the MSC-derived secretome exerts cytoprotective and context-dependent immunomodulatory effects, attenuating inflammatory signaling and cellular stress while supporting the preservation of neural progenitor markers in epileptic tissue. These properties highlight a potential phase-specific therapeutic window to modulate pathological processes during the latent phase of epileptogenesis.<\/jats:p>","DOI":"10.3390\/ijms27010265","type":"journal-article","created":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T00:50:42Z","timestamp":1766969442000},"page":"265","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cytoprotective and Immunomodulatory Properties of Mesenchymal Stem Cell Secretome and Its Effect on Organotypic Hippocampal Cultures in Mouse Model of Temporal Lobe Epilepsy"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0990-1492","authenticated-orcid":false,"given":"Martyna","family":"Strzelec","sequence":"first","affiliation":[{"name":"Department of Transplantation, Faculty of Medicine, Institute of Pediatrics, Jagiellonian University Medical College, 30-663 Krakow, Poland"},{"name":"Doctoral School of Medical and Health Sciences, Jagiellonian University Medical College, 31-530 Krakow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9866-5777","authenticated-orcid":false,"given":"Jan","family":"Detka","sequence":"additional","affiliation":[{"name":"Department of Transplantation, Faculty of Medicine, Institute of Pediatrics, Jagiellonian University Medical College, 30-663 Krakow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0602-0411","authenticated-orcid":false,"given":"Marta","family":"Kot","sequence":"additional","affiliation":[{"name":"Department of Transplantation, Faculty of Medicine, Institute of Pediatrics, Jagiellonian University Medical College, 30-663 Krakow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9477-9073","authenticated-orcid":false,"given":"Qi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Copenhagen, 2200 Copenhagen N, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3231-4667","authenticated-orcid":false,"given":"Ma\u0142gorzata K.","family":"Soboci\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Transplantation, Faculty of Medicine, Institute of Pediatrics, Jagiellonian University Medical College, 30-663 Krakow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9824-7359","authenticated-orcid":false,"given":"Jens D.","family":"Mikkelsen","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Copenhagen, 2200 Copenhagen N, Denmark"},{"name":"Neurobiology Research Unit, University Hospital of Copenhagen, 2100 Copenhagen \u00d8, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0429-681X","authenticated-orcid":false,"given":"Marcin","family":"Majka","sequence":"additional","affiliation":[{"name":"Department of Transplantation, Faculty of Medicine, Institute of Pediatrics, Jagiellonian University Medical College, 30-663 Krakow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1111\/j.1528-1167.2011.03101.x","article-title":"New concepts in classification of the epilepsies: Entering the 21st century: New Concepts in Classification","volume":"52","author":"Berg","year":"2011","journal-title":"Epilepsia"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1055\/s-0040-1718719","article-title":"Epilepsy\u2014Definition, Classification, Pathophysiology, and Epidemiology","volume":"40","year":"2020","journal-title":"Semin. 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