Thermos-responsive hydrogel system encapsulated engineered exosomes attenuate inflammation and oxidative damage in acute spinal cord injury.
Thermos-responsive hydrogel system encapsulated engineered exosomes attenuate inflammation and oxidative damage in acute spinal cord injury.
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包封工程外泌体的热反应水凝胶系统减轻急性脊髓损伤的炎症和氧化损伤。
DOI：
10.3389/fbioe.2023.1216878
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发表时间：
2023
影响因子：
5.7
通讯作者：
Qi Z
中科院分区：
文献类型：
--
作者：
Xiao Y;Hu X;Jiang P;Qi Z
简介：脊髓损伤（SCI）是一种严重的致残性疾病，常规治疗的有效性有限，如支持治疗和急诊手术。来源于脐带间充质干细胞的外泌体（UCMSC-Exos）对SCI具有潜在的治疗作用，但受到递送效率的限制。我们的研究旨在进一步研究miR-138修饰的UCMSC外泌体（Exos-138）在SCI后的治疗作用。 研究方法：我们开发了一种可注射的聚乙醇酸共聚物和聚乙二醇的三嵌段聚合物（PLGA-PEG-PLGA）-负载miR-138修饰的干细胞外泌体的温度敏感性水凝胶，并在体外表征其生物相容性。在患有SCI的Sprague-Dawley大鼠中，将水凝胶注射到损伤部位，测量行为评分，并在术后进行病理学分析以评估神经恢复。 结果如下：在体外，我们的数据表明，miR-138- 5 p修饰的UCMSC-Exos可以通过NLRP 3-caspase 1信号通路降低BV-2细胞中的炎症水平，并通过Nrf 2-keap 1信号级联下调细胞内活性氧水平来减少神经元凋亡。体内实验结果表明，P-Exos-138水凝胶促进了SCI大鼠的神经功能恢复。 讨论：我们的研究探索了一种新的外泌体递送系统，可以成为SCI的潜在治疗策略。我们的研究，目前，具有理论价值;然而，它可以作为进一步研究在炎症依赖性损伤的中枢神经系统的SCI发展的各个阶段的治疗方法的基础。
Introduction: Spinal cord injury (SCI) is a serious and disabling condition, and the effectiveness of conventional treatment is limited, such as supportive treatment and emergency surgery. Exosomes derived from umbilical cord mesenchymal stem cells (UCMSC-Exos) have potential therapeutic effects on SCI but are limited by delivery efficiency. Our study aimed to further investigate the therapeutic effects of miR-138-modified UCMSC-exosomes (Exos-138) following SCI. Methods: We developed an injectable triblock polymer of polyglycolic acid copolymer and polyethylene glycol (PLGA-PEG-PLGA)-loaded temperature-sensitive hydrogel of miR-138-modified stem cell exosomes and characterised its biocompatibility in vitro. In Sprague-Dawley rats with SCI, the hydrogel was injected into the injury site, behavioural scores were measured, and pathological analysis was conducted postoperatively to assess neurological recovery. Results: In vitro, our data demonstrated that miR-138-5p-modified UCMSC-Exos can reduce inflammation levels in BV-2 cells through the NLRP3-caspase1 signalling pathway and reduce neuronal apoptosis by downregulating intracellular reactive oxygen species levels through the Nrf2-keap1 signalling cascade. The results of in vivo experiments showed that the P-Exos-138 hydrogel promoted neurological recovery in rats with SCI. Discussion: Our study explored a novel exosome delivery system that can be a potential therapeutic strategy for SCI. Our study, currently, has theoretical value; however, it can serve as a basis for further investigations on the treatment approaches at various stages of SCI development in inflammation-dependent injury of the central nervous system.
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影响因子：
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作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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影响因子：
9
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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