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间充质干细胞在缺血性脑卒中中的旁分泌作用:机遇与挑战

Paracrine Effects of Mesenchymal Stem Cells in Ischemic Stroke: Opportunities and Challenges.

作者信息

Asgari Taei Afsaneh, Khodabakhsh Pariya, Nasoohi Sanaz, Farahmandfar Maryam, Dargahi Leila

机构信息

Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Department of Neuroscience and Addiction Studies, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

Mol Neurobiol. 2022 Oct;59(10):6281-6306. doi: 10.1007/s12035-022-02967-4. Epub 2022 Aug 3.

DOI:10.1007/s12035-022-02967-4
PMID:35922728
Abstract

It is well acknowledged that neuroprotective effects of transplanted mesenchymal stem cells (MSCs) in ischemic stroke are attributed to their paracrine-mediated actions or bystander effects rather than to cell replacement in infarcted areas. This therapeutic plasticity is due to MSCs' ability to secrete a broad range of bioactive molecules including growth factors, trophic factors, cytokines, chemokines, and extracellular vesicles, overall known as the secretome. The secretome derivatives, such as conditioned medium (CM) or purified extracellular vesicles (EVs), exert remarkable advantages over MSC transplantation in stroke treating. Here, in this review, we used published information to provide an overview on the secretome composition of MSCs, underlying mechanisms of therapeutic effects of MSCs, and preclinical studies on MSC-derived products application in stroke. Furthermore, we discussed current advantages and challenges for successful bench-to-bedside translation.

摘要

众所周知,缺血性中风中移植间充质干细胞(MSCs)的神经保护作用归因于其旁分泌介导的作用或旁观者效应,而非梗死区域的细胞替代。这种治疗可塑性源于MSCs分泌多种生物活性分子的能力,这些分子包括生长因子、营养因子、细胞因子、趋化因子和细胞外囊泡,统称为分泌组。分泌组衍生物,如条件培养基(CM)或纯化的细胞外囊泡(EVs),在中风治疗中比MSC移植具有显著优势。在此综述中,我们利用已发表的信息,概述了MSCs的分泌组组成、MSCs治疗作用的潜在机制以及MSCs衍生产品在中风中应用的临床前研究。此外,我们还讨论了成功实现从 bench 到 bedside 转化的当前优势和挑战。

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Front Neurol. 2025 Apr 15;16:1445962. doi: 10.3389/fneur.2025.1445962. eCollection 2025.
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本文引用的文献

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Emerging roles for the autophagy machinery in extracellular vesicle biogenesis and secretion.自噬机制在细胞外囊泡生物发生和分泌中的新作用。
FASEB Bioadv. 2021 Mar 2;3(5):377-386. doi: 10.1096/fba.2020-00138. eCollection 2021 May.
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Mesenchymal Stem Cell Derived Extracellular Vesicles for Repairing the Neurovascular Unit after Ischemic Stroke.间充质干细胞衍生的细胞外囊泡在缺血性脑卒中后修复神经血管单元。
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Neuroprotective effects of human amniotic fluid stem cells-derived secretome in an ischemia/reperfusion model.
维持缺血性脑卒中血脑屏障完整性:间充质干细胞外泌体成分及潜在分子靶点综述
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Harnessing stem cell therapeutics in LPS-induced animal models: mechanisms, efficacies, and future directions.在脂多糖诱导的动物模型中利用干细胞疗法:作用机制、疗效及未来方向。
Stem Cell Res Ther. 2025 Apr 12;16(1):176. doi: 10.1186/s13287-025-04290-w.
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Conditioned Medium of BMSCs Alleviates HO-Induced Oxidative Damage in PC12 Cells Through the LDLR Pathway.骨髓间充质干细胞条件培养基通过低密度脂蛋白受体途径减轻HO诱导的PC12细胞氧化损伤。
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Microglial polarization pathways and therapeutic drugs targeting activated microglia in traumatic brain injury.创伤性脑损伤中微胶质细胞极化途径及靶向活化微胶质细胞的治疗药物
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Stem cell-derived exosomes for ischemic stroke: a conventional and network meta-analysis based on animal models.基于动物模型的干细胞衍生外泌体治疗缺血性中风:一项传统和网状荟萃分析
Front Pharmacol. 2024 Oct 23;15:1481617. doi: 10.3389/fphar.2024.1481617. eCollection 2024.
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Exosomal miR-486 derived from bone marrow mesenchymal stem cells promotes angiogenesis following cerebral ischemic injury by regulating the PTEN/Akt pathway.骨髓间充质干细胞来源的外泌体 miR-486 通过调控 PTEN/Akt 通路促进脑缺血损伤后血管生成。
Sci Rep. 2024 Aug 5;14(1):18086. doi: 10.1038/s41598-024-69172-2.
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Exosomes derived from bone marrow mesenchymal stem cells harvested from type two diabetes rats promotes neurorestorative effects after stroke in type two diabetes rats.从 2 型糖尿病大鼠骨髓间充质干细胞中提取的外泌体可促进 2 型糖尿病大鼠中风后的神经修复作用。
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