Mesenchymal stem cell (MSC)-derived exosomes are considered as alternative to cell therapy in various diseases. This study aimed to understand the effect of bone marrow MSC-derived exosomes (BMMSC-exos) on spinal cord injury (SCI) and to unveil its regulatory mechanism on ferroptosis. Exosomes were isolated from BMMSCs and the uptake of BMMSCs-exos by PC12 cells was determined using PKH67 staining. The effect of BMMSC-exos on SCI in rats was studied by evaluating pathological changes of spinal cord tissues, inflammatory cytokines, and ferroptosis-related proteins. Transcriptome sequencing was used to discover the differential expressed genes (DEGs) between SCI rats and BMMSC-exos-treated rats followed by functional enrichment analyses. The effect of BMMSC-exos on ferroptosis and interleukin 17 (IL-17) pathway was evaluated in SCI rats and oxygen–glucose deprivation (OGD)-treated PC12 cells. The results showed that particles extracted from BMMSCs were exosomes that could be taken up by PC12 cells. BMMSC-exos treatment ameliorated injuries of spinal cord, suppressed the accumulation of Fe²⁺, malondialdehyde (MDA), and reactive oxygen species (ROS), with the elevated glutathione (GSH). Also, BMMSC-exos downregulated the expression of acyl-CoA synthetase long chain family member 4 (ACSL4) and upregulated glutathione peroxidase 4 (GPX4) and cysteine/glutamate antiporter xCT. A total of 110 DEGs were discovered and they were mainly enriched in IL-17 signaling pathway. Further in vitro and in vivo experiments showed that BMMSC-exos inactivated IL-17 pathway. BMMSC-exos promote the recovery of SCI and inhibit ferroptosis by inhibiting the IL-17 pathway, which provides BMMSC-exos as an alternative to the management of SCI.

间充质干细胞（MSC）衍生的外泌体被认为可以替代多种疾病的细胞疗法。本研究旨在了解骨髓间充质干细胞衍生的外泌体（BMMSC-exos）对脊髓损伤（SCI）的影响，并揭示其对铁死亡的调节机制。从 BMMSC 中分离出外泌体，并使用 PKH67 染色测定 PC12 细胞对 BMMSCs-exos 的摄取。通过评估脊髓组织、炎症细胞因子和铁死亡相关蛋白的病理变化，研究BMMSC-exos对大鼠SCI的影响。使用转录组测序来发现 SCI 大鼠和 BMMSC-exos 处理的大鼠之间的差异表达基因 (DEG)，然后进行功能富集分析。在 SCI 大鼠和氧糖剥夺 (OGD) 处理的 PC12 细胞中评估 BMMSC-exos 对铁死亡和白细胞介素 17 (IL-17) 通路的影响。结果表明，从BMMSCs中提取的颗粒是可以被PC12细胞摄取的外泌体。 BMMSC-exos 治疗可改善脊髓损伤，抑制 Fe ²⁺、丙二醛 (MDA) 和活性氧 (ROS) 的积累，并升高谷胱甘肽 (GSH)。此外，BMMSC-exos 下调酰基辅酶A合成酶长链家族成员 4 (ACSL4) 的表达，上调谷胱甘肽过氧化物酶 4 (GPX4) 和半胱氨酸/谷氨酸逆向转运蛋白 xCT。共发现110个DEG，主要富集于IL-17信号通路。进一步的体外和体内实验表明，BMMSC-exos 灭活了 IL-17 通路。 BMMSC-exos 通过抑制 IL-17 通路促进 SCI 的恢复并抑制铁死亡，这为 BMMSC-exos 提供了作为 SCI 治疗的替代方案。