Li Hengde, Yi Renfeng, Fan Youbing, Zhan Gonghao, Xiao Taoyuan
Department of Spine Surgery, Loudi Central Hospital, Loudi, 417000, China.
Department of Spine Surgery, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
Iran J Basic Med Sci. 2025;28(10):1344-1353. doi: 10.22038/ijbms.2025.85963.18571.
This study aimed to engineer miR-216-overexpressing umbilical cord mesenchymal stem cells (UCMSCs) to generate miR-216-enriched UCMSC-derived exosomes (UCMSC-Exos) and evaluate their therapeutic potential in Spinal cord injury (SCI).
miR-216 overexpression was achieved in UCMSCs, and exosomes were subsequently isolated. The biological effects of miR-216-overexpressing UCMSC-Exos (UCMSC-miR-216-Exos) were assessed using migration, and tube formation assays with vascular endothelial cells. For evaluation, SCI mouse models were treated with either UCMSC-Exos or UCMSC-miR-216-Exos. Functional recovery was measured using the BMS scores, while angiogenesis, neuronal apoptosis, and proinflammatory cytokine expression were analyzed through immunohistochemistry and molecular assays.
qPCR analysis confirmed successful miR-216 overexpression in UCMSCs and their derived exosomes. , UCMSC-miR-216-Exos significantly enhanced endothelial cell migration and tube formation compared to control UCMSC-Exos. , both UCMSC-Exos and UCMSC-miR-216-Exos improved BMS scores, promoted angiogenesis, and reduced neuronal apoptosis and proinflammatory cytokine expression in SCI mice. Notably, UCMSC-miR-216-Exos demonstrated superior therapeutic effects, including greater improvements in functional recovery, enhanced angiogenic responses, and more pronounced reductions in neuronal apoptosis and inflammation compared to control UCMSC-Exos. Additionally, in vitro experiments revealed that PTEN expression was down-regulated, and the AKT pathway was activated following treatment with UCMSC-miR-216-Exos.
These findings demonstrate that miR-216-overexpressing UCMSC-Exos exhibits enhanced therapeutic efficacy in promoting angiogenesis, reducing inflammation and neuronal apoptosis, and improving functional recovery after SCI. This study demonstrates the promise of miR-216-enriched exosomes as a novel cell-free therapeutic approach for SCI, paving the way for clinical translation through their biologically translatable mechanisms.
本研究旨在构建过表达miR-216的脐带间充质干细胞（UCMSC），以产生富含miR-216的UCMSC来源的外泌体（UCMSC-Exos），并评估它们在脊髓损伤（SCI）中的治疗潜力。
在UCMSC中实现miR-216的过表达，随后分离外泌体。使用迁移实验和血管内皮细胞的管形成实验评估过表达miR-216的UCMSC-Exos（UCMSC-miR-216-Exos） 的生物学效应。为了进行评估，用UCMSC-Exos或UCMSC-miR-216-Exos处理SCI小鼠模型。使用BMS评分测量功能恢复情况，同时通过免疫组织化学和分子分析来分析血管生成、神经元凋亡和促炎细胞因子表达。
qPCR分析证实UCMSC及其衍生的外泌体中成功实现了miR-216的过表达。与对照UCMSC-Exos相比，UCMSC-miR-216-Exos显著增强了内皮细胞迁移和管形成。此外，UCMSC-Exos和UCMSC-miR-216-Exos均提高了SCI小鼠的BMS评分，促进了血管生成，并减少了神经元凋亡和促炎细胞因子表达。值得注意的是与对照UCMSC-Exos相比，UCMSC-miR-216-Exos表现出更好的治疗效果，包括功能恢复的更大改善、血管生成反应增强以及神经元凋亡和炎症的更明显减少。此外，体外实验表明，用UCMSC-miR-216-Exos处理后，PTEN表达下调，AKT途径被激活。
这些发现表明，过表达miR-216的UCMSC-Exos在促进血管生成、减少炎症和神经元凋亡以及改善SCI后的功能恢复方面表现出增强的治疗效果。本研究证明了富含miR-216的外泌体作为一种新型的SCI无细胞治疗方法的前景，通过其生物学可转化机制为临床转化铺平了道路。
