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急性呼吸窘迫综合征的细胞治疗

Cell therapy in acute respiratory distress syndrome.

作者信息

Horie Shahd, Gonzalez Hector Esteban, Laffey John G, Masterson Claire H

机构信息

Regenerative Medicine Institute (REMEDI), CÚRAM Centre for Research in Medical Devices, Biomedical Sciences Building, National University of Ireland Galway, Galway, Ireland.

Department of Anesthesia and Intensive Care Medicine, Galway University Hospitals, SAOLTA Hospital Group, Ireland.

出版信息

J Thorac Dis. 2018 Sep;10(9):5607-5620. doi: 10.21037/jtd.2018.08.28.

Abstract

Acute respiratory distress syndrome (ARDS) is driven by a severe pro-inflammatory response resulting in lung damage, impaired gas exchange and severe respiratory failure. There is no specific treatment that effectively improves outcome in ARDS. However, in recent years, cell therapy has shown great promise in preclinical ARDS studies. A wide range of cells have been identified as potential candidates for use, among these are mesenchymal stromal cells (MSCs), which are adult multi-lineage cells that can modulate the immune response and enhance repair of damaged tissue. The therapeutic potential of MSC therapy for sepsis and ARDS has been demonstrated in multiple models. The therapeutic effect of these cells seems to be due to two different mechanisms; direct cellular interaction, and paracrine release of different soluble products such as extracellular vesicles (EVs)/exosomes. Different approaches have also been studied to enhance the therapeutic effect of these cells, such as the over-expression of anti-inflammatory or pro-reparative molecules. Several clinical trials (phase I and II) have already shown safety of MSCs in ARDS and other diseases. However, several translational issues still need to be addressed, such as the large-scale production of cells, and their potentiality and variability, before the therapeutic potential of stem cells therapies can be realized.

摘要

急性呼吸窘迫综合征(ARDS)由严重的促炎反应驱动,导致肺损伤、气体交换受损和严重呼吸衰竭。目前尚无有效改善ARDS预后的特异性治疗方法。然而,近年来,细胞疗法在ARDS临床前研究中显示出巨大潜力。多种细胞已被确定为潜在的治疗候选细胞,其中包括间充质基质细胞(MSCs),它是一种成体多谱系细胞,能够调节免疫反应并促进受损组织的修复。MSC疗法对脓毒症和ARDS的治疗潜力已在多个模型中得到证实。这些细胞的治疗效果似乎归因于两种不同机制:直接细胞相互作用以及不同可溶性产物如细胞外囊泡(EVs)/外泌体的旁分泌释放。人们还研究了多种方法来增强这些细胞的治疗效果,如抗炎或促修复分子的过表达。多项临床试验(I期和II期)已证实MSCs用于ARDS和其他疾病的安全性。然而,在实现干细胞疗法的治疗潜力之前,仍有几个转化问题需要解决,如细胞的大规模生产以及它们的潜能和变异性。

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Cell therapy in acute respiratory distress syndrome.急性呼吸窘迫综合征的细胞治疗
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