Exosomes Derived from Bone Mesenchymal Stem Cells Repair Traumatic Spinal Cord Injury by Suppressing the Activation of A1 Neurotoxic Reactive Astrocytes
Exosomes Derived from Bone Mesenchymal Stem Cells Repair Traumatic Spinal Cord Injury by Suppressing the Activation of A1 Neurotoxic Reactive Astrocytes
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源自骨间充质干细胞的外泌体通过抑制 A1 神经毒性反应性星形胶质细胞的激活来修复创伤性脊髓损伤
DOI：
10.1089/neu.2018.5835
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发表时间：
2019-02-01
影响因子：
4.2
通讯作者：
Cai, Weihua
中科院分区：
文献类型：
--
作者：
Liu, Wei;Wang, Yongxiang;Cai, Weihua
Mesenchymal stem cell (MSC) transplantation is now considered as an effective treatment strategy for traumatic spinal cord injury (SCI). However, several key issues remain unresolved, including low survival rates, cell dedifferentiation, and tumor formation. Recent studies have demonstrated that the therapeutic effect of transplanted stem cells is primarily paracrine mediated. Exosomes are an important paracrine factor that can be used as a direct therapeutic agent. However, there are few reports on the application of exosomes derived from bone MSCs (BMSCs-Exos) in treating SCI. In this study, we demonstrated that BMSCs-Exos possessed robust proangiogenic properties, attenuated neuronal cells apoptosis, suppressed glial scar formation, attenuated lesion size, suppressed inflammation, promoted axonal regeneration, and eventually improved functional behavioral recovery effects after traumatic SCI. Briefly, lesion size was decreased by nearly 60%, neuronal apoptosis was attenuated by nearly 70%, glial scar formation was reduced by nearly 75%, average blood vessel density was increased by nearly 60%, and axonal regeneration was increased by almost 80% at day 28 after SCI in the BMSC-Exos group compared to the control group. Using a series of in vitro functional assays, we also confirmed that treatment with BSMCs-Exos significantly enhanced human umbilical vein endothelial cell proliferation, migration, and angiogenic tubule formation, attenuated neuronal cells apoptosis, and suppressed nitric oxide release in microglia. Moreover, our study demonstrated that administration of BMSCs-Exos suppressed inflammation efficiently after traumatic SCI and suppressed activation of A1 neurotoxic reactive astrocytes. In conclusion, our study suggested that the application of BMSCs-Exos may be a promising strategy for traumatic SCI.
