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微小 RNA 对血管内皮细胞稳态和分化的调控——基于干细胞治疗的血管再生策略的启示。

MicroRNA regulation of endothelial homeostasis and commitment-implications for vascular regeneration strategies using stem cell therapies.

机构信息

Institute of Cardiovascular and Medical Sciences, British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow G12 8TA, UK.

出版信息

Free Radic Biol Med. 2013 Sep;64:52-60. doi: 10.1016/j.freeradbiomed.2013.04.037. Epub 2013 May 9.

Abstract

Human embryonic (hESC) and induced pluripotent (hiPSC) stem cells have broad therapeutic potential in the treatment of a range of diseases, including those of the vascular system. Both hESCs and hiPSCs have the capacity for indefinite self-renewal, in addition to their ability to differentiate into any adult cell type. These cells could provide a potentially unlimited source of cells for transplantation and, therefore, provide novel treatments, e.g. in the production of endothelial cells for vascular regeneration. MicroRNAs are short, noncoding RNAs that act posttranscriptionally to control gene expression and thereby exert influence over a wide range of cellular processes, including maintenance of pluripotency and differentiation. Expression patterns of these small RNAs are tissue specific, and changes in microRNA levels have often been associated with disease states in humans, including vascular pathologies. Here, we review the roles of microRNAs in endothelial cell function and vascular disease, as well as their role in the differentiation of pluripotent stem cells to the vascular endothelial lineage. Furthermore, we discuss the therapeutic potential of stem cells and how knowledge and manipulation of microRNAs in stem cells may enhance their capacity for vascular regeneration.

摘要

人类胚胎(hESC)和诱导多能(hiPSC)干细胞在治疗一系列疾病方面具有广泛的治疗潜力,包括血管系统疾病。hESC 和 hiPSC 除了能够分化为任何成体细胞类型外,还具有无限自我更新的能力。这些细胞可以为移植提供潜在的无限来源的细胞,从而提供新的治疗方法,例如用于血管再生的内皮细胞的产生。microRNAs 是短的非编码 RNA,它们在后转录水平上发挥作用,以控制基因表达,从而对广泛的细胞过程产生影响,包括多能性的维持和分化。这些小 RNA 的表达模式具有组织特异性,并且 microRNA 水平的变化通常与人类的疾病状态有关,包括血管病理学。在这里,我们综述了 microRNAs 在血管内皮细胞功能和血管疾病中的作用,以及它们在多能干细胞向血管内皮谱系分化中的作用。此外,我们讨论了干细胞的治疗潜力,以及对干细胞中的 microRNAs 的了解和操纵如何增强它们的血管再生能力。

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