静脉注射源自人类羊膜间充质干细胞的外泌体可改善大鼠急性创伤性脊髓损伤后的神经功能恢复。

IF 2.1 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Iranian Journal of Basic Medical Sciences Pub Date : 2024-01-01 DOI:10.22038/ijbms.2024.76532.16576
Honglong Zhou, Ji Wang, Peng Zhao, Dongsheng Le, Shanshan Cai, Guohua Mao
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引用次数: 0

摘要

研究目的我们之前的研究表明,移植人羊膜间充质干细胞(hAMSCs)可改善大鼠创伤性脊髓损伤(TSCI)后的神经功能恢复。然而,人们对从 hAMSCs 提取的外泌体对创伤性脊髓损伤的影响知之甚少。在此,我们研究了 hAMSCs 衍生的外泌体是否能改善 TSCI 大鼠的神经功能恢复及其内在机制:使用负重装置建立大鼠创伤性脊髓损伤(TSCI)模式。TSCI后2小时,通过尾静脉给大鼠注射hAMSCs衍生外泌体或磷酸盐缓冲盐水。大鼠的运动恢复情况通过开放场地运动评分量表和网格行走任务进行评估。研究人员对脊髓含水量、苏木精和伊红(H&E)染色、伊文思蓝(EB)染料外渗、免疫荧光染色和酶联免疫吸附进行了检测,以阐明其潜在机制。结果:hAMSCs衍生的外泌体能显著减少ED1+巨噬细胞/小胶质细胞和caspase-3+细胞的数量,降低活性氧、髓过氧化物酶活性和肿瘤坏死因子α、白细胞介素-6和白细胞介素-1β等炎性细胞因子的水平。此外,hAMSCs衍生的外泌体还能显著降低脊髓含水量和埃文斯蓝外渗,促进血管生成和轴突再生。最后,hAMSCs衍生的外泌体还能明显缩小病变体积,抑制星形胶质细胞增生,改善功能恢复:综上所述,这些研究结果表明,hAMSCs衍生的外泌体对急性TSCI后的大鼠具有良好的影响,可作为治疗急性TSCI的另一种无细胞疗法。
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Intravenous administration exosomes derived from human amniotic mesenchymal stem cells improves neurological recovery after acute traumatic spinal cord injury in rats.

Objectives: 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.

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来源期刊
Iranian Journal of Basic Medical Sciences
Iranian Journal of Basic Medical Sciences MEDICINE, RESEARCH & EXPERIMENTAL-PHARMACOLOGY & PHARMACY
CiteScore
4.00
自引率
4.50%
发文量
142
审稿时长
6-12 weeks
期刊介绍: The Iranian Journal of Basic Medical Sciences (IJBMS) is a peer-reviewed, monthly publication by Mashhad University of Medical Sciences (MUMS), Mashhad, Iran . The Journal of "IJBMS” is a modern forum for scientific communication. Data and information, useful to investigators in any discipline in basic medical sciences mainly including Anatomical Sciences, Biochemistry, Genetics, Immunology, Microbiology, Pathology, Pharmacology, Pharmaceutical Sciences, and Physiology, will be published after they have been peer reviewed. This will also include reviews and multidisciplinary research.
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