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Mesenchymal stem cell-derived extracellular vesicle-based therapies protect against coupled degeneration of the central nervous and vascular systems in stroke.
Ageing Research Reviews ( IF 13.1 ) Pub Date : 2020-06-18 , DOI: 10.1016/j.arr.2020.101106
Abolfazl Rahmani 1 , Kiarash Saleki 1 , Nima Javanmehr 1 , Javad Khodaparast 1 , Payam Saadat 2 , Hamid Reza Nouri 3
Affiliation  

Stem cell-based treatments have been suggested as promising candidates for stroke. Recently, mesenchymal stem cells (MSCs) have been reported as potential therapeutics for a wide range of diseases. In particular, clinical trial studies have suggested MSCs for stroke therapy. The focus of MSC treatments has been directed towards cell replacement. However, recent research has lately highlighted their paracrine actions. The secretion of extracellular vesicles (EVs) is offered to be the main therapeutic mechanism of MSC therapy. However, EV-based treatments may provide a wider therapeutic window compared to tissue plasminogen activator (tPA), the traditional treatment for stroke. Exosomes are nano-sized EVs secreted by most cell types, and can be isolated from conditioned cell media or body fluids such as plasma, urine, and cerebrospinal fluid (CSF). Exosomes apply their effects through targeting their cargos such as microRNAs (miRs), DNAs, messenger RNAs, and proteins at the host cells, which leads to a shift in the behavior of the recipient cells. It has been indicated that exosomes, in particular their functional cargoes, play a significant role in the coupled pathogenesis and recovery of stroke through affecting the neurovascular unit (NVU). Therefore, it seems that exosomes could be utilized as diagnostic and therapeutic tools in stroke treatment. The miRs are small endogenous non-coding RNA molecules which serve as the main functional cargo of exosomes, and apply their effects as epigenetic regulators. These versatile non-coding RNA molecules are involved in various stages of stroke and affect stroke-related factors. Moreover, the involvement of aging-induced changes to specific miRs profile in stroke further highlights the role of miRs. Thus, miRs could be utilized as diagnostic, prognostic, and therapeutic tools in stroke. In this review, we discuss the roles of stem cells, exosomes, and their application in stroke therapy. We also highlight the usage of miRs as a therapeutic choice in stroke therapy.



中文翻译:

间充质干细胞衍生的基于细胞外囊泡的疗法可预防中风中枢神经系统和血管系统的变性。

已经提出基于干细胞的治疗有望成为中风的候选药物。近来,间充质干细胞(MSCs)已被报道为多种疾病的潜在治疗方法。特别是,临床试验研究已建议将MSC用于卒中治疗。MSC治疗的重点已转向细胞替代。但是,最近的研究突出了它们的旁分泌作用。细胞外囊泡(EVs)的分泌被认为是MSC治疗的主要治疗机制。但是,与传统的卒中治疗方法组织纤溶酶原激活剂(tPA)相比,基于EV的治疗方法可能提供更大的治疗范围。外来体是大多数细胞类型分泌的纳米级EV,可以从条件细胞培养基或体液(例如血浆,尿液和脑脊髓液(CSF))中分离出来。外泌体通过靶向宿主细胞上的诸如microRNA(miRs),DNA,信使RNA和蛋白质之类的货物来发挥其作用,从而导致受体细胞行为的改变。已经表明,外泌体,特别是其功能性货物,通过影响神经血管单位(NVU)在中风的发病机制和恢复的耦合中起重要作用。因此,似乎外泌体可以用作中风治疗的诊断和治疗工具。miRs是小的内源性非编码RNA分子,可作为外来体的主要功能货物,并发挥其作用作为表观遗传调控因子。这些通用的非编码RNA分子参与中风的各个阶段,并影响中风相关因素。此外,衰老引起的中风特定miRs谱变化的参与进一步凸显了miRs的作用。因此,miRs可以用作中风的诊断,预后和治疗工具。在这篇综述中,我们讨论了干细胞,外泌体的作用及其在中风治疗中的应用。我们还强调了miRs在中风治疗中作为治疗选择的用途。

更新日期:2020-06-18
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