Zheng Yitong, Wang Yongxin, Liu Wen, A Mujite, Li Yabin, Ma Xiaohu, Abulimiti Mieradili, Maimaitiaili Nuerailijiang, Qin Hu
Department of Neurosurgery, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region 830000, P.R. China.
Exp Ther Med. 2025 Jan 22;29(3):57. doi: 10.3892/etm.2025.12807. eCollection 2025 Mar.
Spinal cord injury (SCI) is a severe condition that often leads to permanent functional impairments. The current treatment options are limited and there is a need for more effective treatments. Human umbilical cord mesenchymal stem cells (hUCMSCs) have shown promise in promoting neuroregeneration and modulating immune response. In addition, miR-124-3p has been identified as a potential biomarker for monitoring the progress of neural repair, making it a focus of the present study, which used a rat model of SCI to evaluate the effects of intrathecal hUCMSC transplantation. The present study included three groups: A sham-operated group, an SCI model group receiving PBS and an SCI group receiving hUCMSCs. Neurological function was assessed using the Basso, Beattie and Bresnahan locomotor rating scale and Rivlin inclined plane test on days 1, 3, 7, 14 and 21 post-injury. Histological analysis included hematoxylin and eosin staining to assess tissue morphology, Nissl staining to evaluate neuron survival and immunofluorescence to detect bromodeoxyuridine (BrdU)+/neuron-specific enolase (NSE)+ cells, which indicate neurogenesis. Detection of brain-derived neurotrophic factor (BDNF) protein expression at various time points in rats with spinal cord injury using western blotting. miR-124-3p expression was quantified using reverse transcription-quantitative (RT-q)PCR to assess its potential as a biomarker for SCI recovery. The hUCMSC group showed significant improvements in motor function compared with the control group, particularly on days 7 and 14 post-injury. Histological analysis revealed reduced scar tissue formation and increased neuron survival in the hUCMSC group. Immunofluorescence analysis showed a higher number of BrdU+/NSE+ cells in the hUCMSC group, indicating enhanced neurogenesis. The expression of the neurorepair-related protein BDNF was markedly higher in the hUCMSCs group compared with the control group. Furthermore, RT-qPCR analysis demonstrated a marked upregulation of miR-124-3p in the hUCMSC group, which was correlated with improved functional recovery. The present study demonstrated that intrathecal transplantation of hUCMSCs notably enhanced recovery following SCI, probably by promoting neurogenesis and modulating miR-124-3p expression. miR-124-3p upregulation in the hUCMSC group highlighted its potential as a biomarker for tracking the progress of SCI recovery. These findings provided a foundation for the future clinical applications of hUCMSCs in SCI treatment and the use of miR-124-3p as a monitoring tool.
脊髓损伤（SCI）是一种严重疾病，常导致永久性功能障碍。目前的治疗选择有限，需要更有效的治疗方法。人脐带间充质干细胞（hUCMSCs）在促进神经再生和调节免疫反应方面已显示出前景。此外，miR-124-3p已被确定为监测神经修复进程的潜在生物标志物，这使其成为本研究的重点。本研究使用SCI大鼠模型评估鞘内注射hUCMSC移植的效果。本研究包括三组：假手术组、接受PBS的SCI模型组和接受hUCMSCs的SCI组。在损伤后第1、3、7、14和21天，使用Basso、Beattie和Bresnahan运动评分量表以及Rivlin斜面试验评估神经功能。组织学分析包括苏木精-伊红染色以评估组织形态、尼氏染色以评估神经元存活以及免疫荧光以检测5-溴脱氧尿嘧啶核苷（BrdU）+/神经元特异性烯醇化酶（NSE）+细胞，这些细胞表明神经发生。使用蛋白质免疫印迹法检测脊髓损伤大鼠在各个时间点脑源性神经营养因子（BDNF）蛋白的表达。使用逆转录定量（RT-q）PCR对miR-124-3p表达进行定量，以评估其作为SCI恢复生物标志物的潜力。与对照组相比，hUCMSC组的运动功能有显著改善，尤其是在损伤后第7天和第14天。组织学分析显示hUCMSC组瘢痕组织形成减少，神经元存活增加。免疫荧光分析显示hUCMSC组中BrdU+/NSE+细胞数量更多，表明神经发生增强。与对照组相比，hUCMSCs组中神经修复相关蛋白BDNF的表达明显更高。此外，RT-qPCR分析表明hUCMSC组中miR-124-3p明显上调，这与功能恢复改善相关。本研究表明，鞘内注射hUCMSCs显著促进了SCI后的恢复，可能是通过促进神经发生和调节miR-124-3p表达实现的。hUCMSC组中miR-124-3p上调突出了其作为追踪SCI恢复进程生物标志物的潜力。这些发现为hUCMSCs在SCI治疗中的未来临床应用以及将miR-124-3p用作监测工具提供了基础。
