Deparment of Neurology, University of Göttingen Medical School, Göttingen, Lower Saxony, Germany.
Deparment of Neurology, University Hospital Giessen, Giessen, Hesse, Germany.
Stem Cells Transl Med. 2023 Nov 3;12(11):707-713. doi: 10.1093/stcltm/szad055.
Various preclinical stroke models have demonstrated the neuroprotective effects of extracellular vesicles (EVs) obtained from several types of cells, including neurons, astrocytes, microglia, neuronal progenitor cells, bone marrow stem cells, and mesenchymal stem cells. EVs interfere with key mechanisms in stroke pathophysiology such as cell death, neuroinflammation, autophagy, and angiogenesis. The mode of action and efficacy depend on the specific EV content, including miRNAs, proteins, and lipids, which can be modified through (I) bioengineering methods, (II) choice of source cells, and (III) modification of the source cell environment. Indeed, modifying the environment by preconditioning the EV-secreting cells with oxygen-glucose deprivation or medium modification revealed superior neuroprotective effects in stroke models. Although the concept of preconditioned EVs is relatively novel, it holds promise for the future treatment of ischemic stroke. Here, we give a brief overview about the main mechanisms of EV-induced neuroprotection and discuss the current status of preconditioning concepts for EV-treatment of ischemic stroke.
各种临床前中风模型已经证明了从几种类型的细胞(包括神经元、星形胶质细胞、小胶质细胞、神经元祖细胞、骨髓干细胞和间充质干细胞)获得的细胞外囊泡(EVs)具有神经保护作用。EVs 干扰中风病理生理学中的关键机制,如细胞死亡、神经炎症、自噬和血管生成。作用模式和疗效取决于特定的 EV 含量,包括 miRNA、蛋白质和脂质,这些可以通过(I)生物工程方法、(II)选择源细胞和(III)修饰源细胞环境来修饰。事实上,通过用氧葡萄糖剥夺或培养基修饰来预处理 EV 分泌细胞来修饰环境,在中风模型中显示出更好的神经保护作用。尽管预处理 EV 的概念相对较新,但它为缺血性中风的未来治疗提供了希望。在这里,我们简要概述了 EV 诱导的神经保护的主要机制,并讨论了预处理概念在 EV 治疗缺血性中风中的现状。