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Mesenchymal Stem Cells for Ischemic Stroke: Progress and Possibilities

机译:用于缺血性卒中的间充质干细胞:进展和可能性

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Abstract: Stroke is the most common neurological cause of morbidity and mortality in industrialized countries, afflicting 15 million people every year. The numbers are expected to increase, mostly due to aging populations. One in five stroke patients dies, and one in three are left with permanent disabilities. Although some acute phase therapies such as intravenous recombinant tissue plasminogen activator (rt-PA) andendovascular treatment have been shown to improve ischemic stroke outcome, these therapies are available only for a small proportion of patients. The use of stem cells to replace brain cells lost during stroke is a long-term goal, and one which is difficult to achieve given that transplanted cells must integrate and restore neural pathways to regain function of damaged parts of the brain. Over the past decade the use of mesenchymal stromal cells (MSCs) as therapy has emerged as a particularly attractive option. MSCs are a class of multipotent, self-renewing cells that give rise to differentiated progeny when implanted into appropriate tissues. Herein, we present a review of the application of MSCs in ischemic stroke, including the source of MSCs, the route and timing of their delivery into the brain and the endpoints measured. Experimental data of transplantation of MSCs in animal stroke models suggest an improved functional recovery. The transplantation of MSCs influences a wide range of events by modulating the inflammatory environment, stimulating endogenous neurogenesis and angiogenesis and reducing the formation of glial scar, although the precise, underlying mechanism of this phenomenon remains unknown. The results from early clinical trials highlight the need to optimize variables such as cell selection and route of administration in order to translate these results into safe and successful clinical applications.
机译:摘要:中风是工业化国家的发病率和死亡率最常见的神经原因,每年折磨1500万人。这些数字预计会增加,主要是由于老龄化人口。五分之一的中风患者死亡,其中三分之一留下了永久性残疾。虽然已经显示出一些急性相疗法,例如静脉注射复合组织纤溶酶原激活剂(RT-PA)吞咽血管治疗,但是这些疗法仅用于少比例患者。使用干细胞替代脑卒中期间损失的脑细胞是长期目的,并且难以达到移植的细胞必须整合和恢复神经途径以重新获得大脑损坏部位的功能。在过去的十年中,使用间充质基质细胞(MSC)作为疗法的使用是特别有吸引力的选择。 MSCS是一类多能的自我更新细胞,当植入适当的组织时会产生分化的后代。在此,我们介绍了MSCs在缺血性卒中中的应用,包括MSC的来源,其输送到脑中的途径,途径和测量的终点。动物卒中模型中MSCs移植的实验数据表明功能恢复改善。 MSC的移植通过调节炎性环境,刺激内源神经发生和血管生成并减少胶质瘢痕的形成,尽管这种现象的精确机制仍然未知。早期临床试验的结果突出了优化诸如细胞选择和给药途径的变量的需要,以便将这些结果转化为安全和成功的临床应用。

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