Zhou Honglong, Wang Ji, Zhao Peng, Le Dongsheng, Cai Shanshan, Mao Guohua
Department of Neurosurgery, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, China.
These authors contributed eqully to this work.
Iran J Basic Med Sci. 2024;27(10):1284-1292. doi: 10.22038/ijbms.2024.76532.16576.
Our previous study has showed that human amniotic mesenchymal stem cells (hAMSCs) transplantation improves neurological recovery after traumatic spinal cord injury (TSCI) in rats. However, less is known about the effects of exosomes derived from hAMSCs for TSCI. Here, we investigated whether hAMSCs-derived exosomes improve neurological recovery in TSCI rats and the underlying mechanisms.
A rat traumatic spinal cord injury (TSCI) mode was established using a weight drop device. At 2 hr after TSCI, rats were administered either hAMSCs-derived exosomes or phosphate buffered saline via the tail vein. Locomotor recovery was evaluated by an open-field locomotor rating scale and gridwalk task. Spinal cord water content, hematoxylin and eosin (H&E) staining, Evans blue (EB) dye extravasation, immunofluorescence staining, and enzyme-linked immunosorbent were performed to elucidate the underlying mechanism.
hAMSCs-derived exosomes significantly reduced the numbers of ED1 macrophages/microglia and caspase-3+cells and decreased the levels of reactive oxygen species, myeloperoxidase activity and inflammatory cytokines, such as tumor necrosis factor alpha, interleukin-6 and interleukin-1β. In addition, hAMSCs-derived exosomes significantly attenuated spinal cord water content and Evans blue extravasation, and enhanced angiogenesis and axonal regeneration. Finally, hAMSCs-derived exosomes also significantly reduced the lesion volume, inhibited astrogliosis, and improved functional recovery.
Taken together, these findings demonstrate that hAMSCs-derived exosomes have favourable effects on rats after acute TSCI, and that they may serve as an alternative cell-free therapeutic approach for treating acute TSCI.
我们之前的研究表明,人羊膜间充质干细胞(hAMSCs)移植可改善大鼠创伤性脊髓损伤(TSCI)后的神经功能恢复。然而,关于hAMSCs来源的外泌体对TSCI的影响知之甚少。在此,我们研究了hAMSCs来源的外泌体是否能改善TSCI大鼠的神经功能恢复及其潜在机制。
使用重物坠落装置建立大鼠创伤性脊髓损伤(TSCI)模型。TSCI后2小时,通过尾静脉给大鼠注射hAMSCs来源的外泌体或磷酸盐缓冲盐水。通过旷场运动评分量表和网格行走任务评估运动功能恢复情况。进行脊髓含水量、苏木精-伊红(H&E)染色、伊文思蓝(EB)染料外渗、免疫荧光染色和酶联免疫吸附测定以阐明潜在机制。
hAMSCs来源的外泌体显著减少了ED1巨噬细胞/小胶质细胞和caspase-3+细胞的数量,降低了活性氧水平、髓过氧化物酶活性以及肿瘤坏死因子α、白细胞介素-6和白细胞介素-1β等炎性细胞因子的水平。此外,hAMSCs来源的外泌体显著减轻了脊髓含水量和伊文思蓝外渗,增强了血管生成和轴突再生。最后,hAMSCs来源的外泌体还显著减小了损伤体积,抑制了星形胶质细胞增生,并改善了功能恢复。
综上所述,这些发现表明hAMSCs来源的外泌体对急性TSCI后的大鼠具有有益作用,并且它们可能作为一种无细胞治疗方法用于治疗急性TSCI。