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间充质干细胞在急性呼吸窘迫综合征中的治疗益处的当前认识。

Current understanding of the therapeutic benefits of mesenchymal stem cells in acute respiratory distress syndrome.

作者信息

Lopes-Pacheco Miquéias, Robba Chiara, Rocco Patricia Rieken Macêdo, Pelosi Paolo

机构信息

Laboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.

National Institute of Science and Technology for Regenerative Medicine, Rio de Janeiro, Brazil.

出版信息

Cell Biol Toxicol. 2020 Feb;36(1):83-102. doi: 10.1007/s10565-019-09493-5. Epub 2019 Sep 4.

Abstract

The acute respiratory distress syndrome (ARDS) is a multifaceted lung disorder in which no specific therapeutic intervention is able to effectively improve clinical outcomes. Despite an improved understanding of molecular mechanisms and advances in supportive care strategies, ARDS remains associated with high mortality, and survivors usually face long-term morbidity. In recent years, preclinical studies have provided mounting evidence of the potential of mesenchymal stem cell (MSC)-based therapies in lung diseases and critical illnesses. In several models of ARDS, MSCs have been demonstrated to induce anti-inflammatory and anti-apoptotic effects, improve epithelial and endothelial cell recovery, and enhance microbial and alveolar fluid clearance, thus resulting in improved lung and distal organ function and survival. Early-stage clinical trials have also demonstrated the safety of MSC administration in patients with ARDS, but further, large-scale investigations are required to assess the safety and efficacy profile of these therapies. In this review, we summarize the main mechanisms whereby MSCs have been shown to exert therapeutic effects in experimental ARDS. We also highlight questions that need to be further elucidated and barriers that must be overcome in order to efficiently translate MSC research into clinical practice.

摘要

急性呼吸窘迫综合征(ARDS)是一种多方面的肺部疾病,目前尚无特异性治疗干预措施能够有效改善临床结局。尽管对分子机制的认识有所提高,支持治疗策略也取得了进展,但ARDS的死亡率仍然很高,幸存者通常面临长期的并发症。近年来,临床前研究提供了越来越多的证据,表明基于间充质干细胞(MSC)的疗法在肺部疾病和危重病中的潜力。在几种ARDS模型中,已证明间充质干细胞可诱导抗炎和抗凋亡作用,改善上皮和内皮细胞恢复,并增强微生物和肺泡液清除,从而改善肺和远端器官功能及生存率。早期临床试验也证明了在ARDS患者中给予间充质干细胞的安全性,但需要进一步进行大规模研究以评估这些疗法的安全性和有效性。在本综述中,我们总结了间充质干细胞在实验性ARDS中发挥治疗作用的主要机制。我们还强调了为了将间充质干细胞研究有效地转化为临床实践需要进一步阐明的问题和必须克服的障碍。

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