Objective The therapeutic benefits of exosomes obtained from mesenchymal stem cells (MSCs) in acute spinal cord injury (SCI) have been demonstrated in recent years, but the precise mechanisms remain unknown. In this study, the efficacy and mechanisms of MSC-derived exosomes (MSC-Exo) in acute SCI were investigated.
Methods By utilizing a BV2 ferroptosis cellular model and an SCI rat model, we investigated the effects of MSC-Exo on iron death related indicators and NF-E2 related factor 2 (Nrf2)/GTP cyclolase I (GCH1)/5,6,7,8-tetrahydrobiopterin (BH4) signaling axis, as well as their therapeutic effects on SCI rats.
Results The results revealed that MSC-Exo effectively inhibited the production of ferrous iron, lipid peroxidation products malonaldehyde and reactive oxygen species, and ferroptosis-promoting factor prostaglandin-endoperoxide synthase 2. Concurrently, they upregulated ferroptosis suppressors FTH-1 (ferritin heavy chain 1), SLC7A11 (solute carrier family 7 member 11), FSP1 (ferroptosis suppressor protein 1), and GPX4 (glutathione peroxidase 4), contributing to enhanced neurological recovery in SCI rats. Further analysis showed the Nrf2/GTP/BH4 signaling pathway’s critical role in suppressing ferroptosis. Additionally, MSC-Exo was found to inhibit lipopolysaccharide-induced ferroptosis in BV2 cells and SCI rats by activating the Nrf2/GCH1/BH4 axis.
Conclusion In summary, the study demonstrates that MSC-Exo mitigates microglial cell ferroptosis via the Nrf2/GCH1/BH4 axis, showing potential for preserving and restoring neurological function post-SCI.
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Objective Exosomes in the central nervous system (CNS) have become an attractive area of research with great value. However, few bibliometric analysis has been conducted. The study aimed to visualize the scientific trends and research hotspots of exosomes in the CNS by bibliometric analysis.
Methods All potential articles and reviews on exosomes in the CNS published in English from 2001 to 2021 were extracted from the Web of Science Core Collection. The visualization knowledge maps of critical indicators, including countries/regions, institutions, authors, journals, references, and keywords, were generated by CiteSpace and VOSviewer software. Besides, each domain's quantitative and qualitative analysis was also considered.
Results A total of 2,629 papers were included. The number of exosomes-related publications and citations regarding CNS increased yearly. These publications came from 2,813 institutions in 77 countries/regions, led by the United States and China. Harvard University was the most influential institution, while the National Institutes of Health was the most critical funding source. We identified 14,468 authors, among which Kapogiannis D had the most significant number of articles and the highest H-index, while Théry C was the most frequently co-cited. The cluster analysis of keywords generated 13 clusters. In summary, the topic of biogenesis, biomarker, and drug delivery will serve as hotspots in future research.
Conclusion Exosomes-related CNS research has gained considerable attention in the past 20 years. The sources and biological functions of exosomes and their promising role in diagnosing and treating CNS diseases are considered hotspots in this field. The clinical translation of the results from exosomes-related CNS research will be of great importance in the future.
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