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Integr. Neurosci."],"abstract":"<jats:p>Background:The precise pathological mechanisms driving Parkinson\u2019s disease (PD) progression remain incompletely understood, and there are currently no therapies that can modify the course of the disease. While mesenchymal stem cells (MSCs) hold therapeutic potential for various conditions, their clinical utility is constrained by challenges in sourcing and limited availability.Methods:This study investigated a novel therapeutic approach using trophoblast-derived mesenchymal-like stem cells (T-MSCs), which can be stably generated from commercially available embryonic stem cells, and the small extracellular vesicles (T-MSCs-sEVs) that they secrete. We explored the therapeutic effects against PD by inhibiting Caspase-8\/Caspase-3-mediated apoptosis both in vitro and in vivo using experimental assays (e.g., flow cytometry (FCM) analysis, western blotting, and immunofluorescence staining).Results:The selected cytokine Clusterin was validated via G-Series Mouse Cytokine Antibody Array 4000 (GSM-CAA-4000) using ELISA kits, which revealed its involvement in apoptosis during the PD process. Moreover, T-MSCs and T-MSCs-sEVs could alleviate dopaminergic (DA) neuron damage in vitro and in vivo by inhibiting the Caspase-8\/Caspase-3-mediated apoptotic pathway.Conclusions:The results suggest that T-MSCs-sEVs represent a promising biological candidate for future therapeutic strategies aimed at treating PD.<\/jats:p>","DOI":"10.31083\/jin49659","type":"journal-article","created":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T10:18:12Z","timestamp":1783419492000},"source":"Crossref","is-referenced-by-count":0,"title":["Small Extracellular Vesicles Derived From Mesenchymal Stem Cells Exert Neuroprotective Effect Against a Model of Dopamine Dysfunction by Inhibiting Caspase-8\/Caspase-3-Mediated Apoptosis"],"prefix":"10.31083","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6096-5168","authenticated-orcid":true,"given":"Songzhe","family":"He","sequence":"first","affiliation":[{"name":"Department of Neurology, Nanfang Hospital, Southern Medical University, 510515 Guangzhou, Guangdong, China"},{"name":"Key Laboratory of Mental Health of the Ministry of Education, Southern Medical University, 510515 Guangzhou, Guangdong, China"},{"name":"Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, 510515 Guangzhou, Guangdong, China"},{"name":"Department of Clinic Laboratory, The First Affiliated Hospital of Guilin Medical University, 541001 Guilin, Guangxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5147-4359","authenticated-orcid":true,"given":"Qi","family":"Qu","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, 510515 Guangzhou, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4950-726X","authenticated-orcid":true,"given":"Ling","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Ganzhou Hospital-Nanfang Hospital, Southern Medical University, 341000 Ganzhou, Jiangxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4217-9726","authenticated-orcid":true,"given":"Yufang","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Neurology, Ganzhou Hospital-Nanfang Hospital, Southern Medical University, 341000 Ganzhou, Jiangxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2218-8781","authenticated-orcid":true,"given":"Qiongqiong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Nanfang Hospital, Southern Medical University, 510515 Guangzhou, Guangdong, China"},{"name":"Key Laboratory of Mental Health of the Ministry of Education, Southern Medical University, 510515 Guangzhou, Guangdong, China"},{"name":"Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, 510515 Guangzhou, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7833-7095","authenticated-orcid":true,"given":"Yi","family":"Ouyang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Ganzhou Hospital-Nanfang Hospital, Southern Medical University, 341000 Ganzhou, Jiangxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2911-0161","authenticated-orcid":true,"given":"Xiaofang","family":"Wang","sequence":"additional","affiliation":[{"name":"ImStem Biotechnology, Inc., Farmington, CT 06030, USA"},{"name":"ZhuHai Hengqin ImStem Biotechnology Co., Ltd., 519000 Zhuhai, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0647-3701","authenticated-orcid":true,"given":"Shaogang","family":"Qu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Ganzhou Hospital-Nanfang Hospital, Southern Medical University, 341000 Ganzhou, Jiangxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"16242","published-online":{"date-parts":[[2026,6,22]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","unstructured":"Liu J, Liu W, Yang H. 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