Intravenous administration exosomes derived from human amniotic mesenchymal stem cells improves neurological recovery after acute traumatic spinal cord injury in rats

Abstract

Objective(s): 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. Materials and Methods: 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.Results: 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. Conclusion: 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.

Keywords

• angiogenesis
• exosomes
• mesenchymal stem cells
• neural regeneration
• recovery of function