{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T05:10:31Z","timestamp":1780463431840,"version":"3.54.1"},"reference-count":102,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Spinal cord injury (SCI) is a devastating neurological condition with limited regenerative capacity. Stem cell\u2013based approaches have emerged as promising strategies due to their neuroprotective and immunomodulatory properties, largely mediated by small extracellular vesicles (sEVs) and their molecular cargo, including miRNAs. In this study, we aimed to evaluate the neuroprotective and anti-apoptotic potential of sEVs derived from SPC-01 and iMR-90 neural stem cell sources using an\n                      <jats:italic>in vitro<\/jats:italic>\n                      rat model of SCI.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      sEVs were isolated from SPC-01 and iMR-90 culture media and characterized by MADLS and Western blot. Spinal cord slices (SCS) were used as an\n                      <jats:italic>in vitro<\/jats:italic>\n                      SCI model with three groups: control, SCI, and SCI treated with sEVs. Injury was induced at 18\u201320\u202fdays\n                      <jats:italic>in vitro<\/jats:italic>\n                      , followed by immediate sEV application. After 72\u202fh, tissue samples were collected and analyzed to assess proteins associated with apoptosis, cytoskeletal integrity, and survival signaling pathways.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>SCI induced cytoskeletal disruption and increased apoptotic markers. sEV treatment attenuated these changes, reducing injury-associated proteins toward baseline levels. Both SPC-01- and iMR-90-derived sEVs showed neuroprotective effects. This was associated with modulation of key pathways, including decreased PTEN, increased STAT3 phosphorylation, and elevated Bcl-xL. Reduced Nogo-A and normalized RhoA levels further indicate attenuation of inhibitory signaling and improved cytoskeletal stability. Overall, sEVs promoted early neuroprotective responses and reduced pathology-associated protein expression in the SCI model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      Neural stem cell-derived sEVs promote neuroprotection\n                      <jats:italic>in vitro<\/jats:italic>\n                      by modulating PTEN\/STAT3 signaling, reducing apoptosis, and stabilizing cytoskeletal dynamics. Although limited to early injury responses in an\n                      <jats:italic>in vitro<\/jats:italic>\n                      model, these findings support sEVs as a promising cell-free therapeutic strategy for SCI.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fncel.2026.1835240","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T04:52:46Z","timestamp":1780462366000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Neural stem cell-derived extracellular vesicles drive early neuroprotective and anti-apoptotic responses in spinal cord injury organotypic slices"],"prefix":"10.3389","volume":"20","author":[{"given":"Kristyna","family":"Sintakova","sequence":"first","affiliation":[{"name":"Department of Neuroregeneration, Institute of Experimental Medicine of the Czech Academy of Sciences","place":["Prague, Czechia"]},{"name":"Second Faculty of Medicine, Charles University","place":["Prague, Czechia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vojtech","family":"Sprincl","sequence":"additional","affiliation":[{"name":"Department of Neuroregeneration, Institute of Experimental Medicine of the Czech Academy of Sciences","place":["Prague, Czechia"]},{"name":"Second Faculty of Medicine, Charles University","place":["Prague, Czechia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Arzhanov","sequence":"additional","affiliation":[{"name":"Department of Neuroregeneration, Institute of Experimental Medicine of the Czech Academy of Sciences","place":["Prague, Czechia"]},{"name":"Second Faculty of Medicine, Charles University","place":["Prague, Czechia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruslan","family":"Klassen","sequence":"additional","affiliation":[{"name":"Laboratory of Glial Biology and Omics Technologies, Institute of Biotechnology of the Czech Academy of Sciences \u2013 BIOCEV","place":["Vestec, Czechia"]},{"name":"Department of Biochemistry and Microbiology, Faculty of Food and Biochemical Technology, UCT Prague","place":["Prague, Czechia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lukas","family":"Valihrach","sequence":"additional","affiliation":[{"name":"Laboratory of Glial Biology and Omics Technologies, Institute of Biotechnology of the Czech Academy of Sciences \u2013 BIOCEV","place":["Vestec, Czechia"]},{"name":"GeneCore Facility, Institute of Biotechnology of the Czech Academy of Sciences \u2013 BIOCEV","place":["Vestec, Czechia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nataliya","family":"Romanyuk","sequence":"additional","affiliation":[{"name":"Department of Neuroregeneration, Institute of Experimental Medicine of the Czech Academy of Sciences","place":["Prague, Czechia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,3]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"105069","DOI":"10.1016\/j.phrs.2020.105069","article-title":"Targeting apoptosis and autophagy following spinal cord injury: therapeutic approaches to polyphenols and candidate phytochemicals","volume":"160","author":"Abbaszadeh","year":"2020","journal-title":"Pharmacol. 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