Intrathecal transplantation of human umbilical cord mesenchymal stem cells enhances spinal cord injury recovery: Role of miR‑124‑3p as a biomarker.

IF 2.3 Experimental and therapeutic medicine Pub Date : 2025-01-22 eCollection Date: 2025-03-01 DOI:10.3892/etm.2025.12807
Yitong Zheng, Yongxin Wang, Wen Liu, Mujite A, Yabin Li, Xiaohu Ma, Mieradili Abulimiti, Nuerailijiang Maimaitiaili, Hu Qin
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Abstract

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.

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人脐带间充质干细胞鞘内移植促进脊髓损伤恢复:miR - 124 - 3p作为生物标志物的作用
脊髓损伤(SCI)是一种严重的疾病,通常会导致永久性的功能损伤。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显示出前景。此外,miR-124-3p已被确定为监测神经修复进展的潜在生物标志物,使其成为本研究的重点,本研究使用脊髓损伤大鼠模型来评估鞘内hUCMSC移植的效果。本研究分为三组:假手术组、PBS治疗的SCI模型组和hUCMSCs治疗的SCI组。分别于伤后第1、3、7、14、21天采用Basso、Beattie和Bresnahan运动评定量表和Rivlin斜面测验评估神经功能。组织学分析包括苏木精染色和伊红染色评估组织形态,尼氏染色评估神经元存活,免疫荧光检测溴脱氧尿苷(BrdU)+/神经元特异性烯醇化酶(NSE)+细胞,表明神经发生。western blot检测脊髓损伤大鼠脑源性神经营养因子(BDNF)蛋白在不同时间点的表达。使用逆转录定量(RT-q)PCR对miR-124-3p的表达进行量化,以评估其作为脊髓损伤恢复的生物标志物的潜力。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BrdU+/NSE+细胞数量增加,表明神经发生增强。与对照组相比,hUCMSCs组神经修复相关蛋白BDNF的表达明显升高。此外,RT-qPCR分析显示,在hUCMSC组中miR-124-3p显著上调,这与功能恢复的改善有关。本研究表明,鞘内移植hUCMSCs可显著增强脊髓损伤后的恢复,可能是通过促进神经发生和调节miR-124-3p表达。hUCMSC组中miR-124-3p的上调突出了其作为跟踪SCI恢复进展的生物标志物的潜力。这些发现为未来hUCMSCs在SCI治疗中的临床应用以及miR-124-3p作为监测工具提供了基础。
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