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.
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.
Where did the research take place?
The study site has not been established. Author addresses may differ from where the research occurred.
Guangzhou, CN · Author affiliation
Department of Neurology, Nanfang Hospital, Southern Medical University, 510515 Guangzhou, Guangdong, China.Location evidence
HK · Author affiliation · country only
Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, 510515 Guangzhou, Guangdong, China.Location evidence
MO · Author affiliation · country only
Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, 510515 Guangzhou, Guangdong, China.Location evidence
Guilin, CN · Author affiliation
Department of Clinic Laboratory, The First Affiliated Hospital of Guilin Medical University, 541001 Guilin, Guangxi, China.Location evidence
Ganzhou, CN · Author affiliation
Department of Neurology, Ganzhou Hospital-Nanfang Hospital, Southern Medical University, 341000 Ganzhou, Jiangxi, China.Location evidence
Jiangxi, CN · Author affiliation
Department of Neurology, Ganzhou Hospital-Nanfang Hospital, Southern Medical University, 341000 Ganzhou, Jiangxi, China.Location evidence
US · Author affiliation · country only
ImStem Biotechnology, Inc., Farmington, CT 06030, USA.Location evidence
CN · Author affiliation · country only
ZhuHai Hengqin ImStem Biotechnology Co., Ltd., 519000 Zhuhai, Guangdong, China.Location evidence
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Original abstract
BACKGROUND: The precise pathological mechanisms driving Parkinson's 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.