■我们先前的研究表明,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)后的神经系统恢复。然而,关于源自hAMSCs的外泌体对TSCI的影响知之甚少。这里,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.
■使用减重装置建立大鼠创伤性脊髓损伤(TSCI)模式。在TSCI后2小时,通过尾静脉给予大鼠hAMSC来源的外泌体或磷酸盐缓冲盐水。通过开场运动评分量表和gridwalk任务评估运动恢复。脊髓含水量,苏木精和伊红(H&E)染色,伊文思蓝(EB)染料外渗,免疫荧光染色,和酶联免疫吸附来阐明潜在的机制。
■hAMSCs来源的外泌体显着减少了ED1巨噬细胞/小胶质细胞和caspase-3细胞的数量,并降低了活性氧的水平,髓过氧化物酶活性和炎症细胞因子,比如肿瘤坏死因子α,白细胞介素-6和白细胞介素-1β。此外,hAMSCs来源的外泌体显着减弱脊髓水含量和伊文思蓝外渗,增强血管生成和轴突再生。最后,hAMSCs来源的外泌体也显著减少病变体积,抑制星形胶质增生,改善功能恢复。
■放在一起,这些发现表明,hAMSCs来源的外泌体对急性TSCI后的大鼠有良好的疗效,并且它们可以作为治疗急性TSCI的替代无细胞治疗方法.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.