间充质干细胞治疗ARDS的新观点

doi:10.3969/j.issn.1674-490X.2018.05.002

摘要/Abstract

摘要： 急性呼吸窘迫综合征(acute respiratory distress syndrome,ARDS)多由重症感染和肺损伤引起,可导致呼吸衰竭,病死率高,目前尚无特效治疗。间充质干细胞(mesenchymal stem cells,MSCs)是成体多潜能干细胞,可调节机体免疫反应,促进受损组织修复,使其治疗ARDS成为可能。动物实验显示MSCs可减轻细菌性肺炎和缺血再灌注诱导的肺损伤,促进呼吸机相关肺损伤的修复。MSCs可抑制机体的炎性反应、增强机体对细菌感染的抵抗力。MSCs通过多种机制发挥治疗效应,如细胞间的相互作用、可溶性因子和外泌体的旁分泌功能等。促进MSCs高表达抗炎分子和促修复分子,能增强其治疗效果。MSCs治疗ARDS已进入临床试验,其结果显示机体具有良好耐受性。尽管目前MSCs要实现大规模移植仍存在很多问题,如细胞的大量培养、细胞的效价和批次的差异等,但MSCs独特的生物学效应,使其成为治疗ARDS最有希望的一类干细胞。

关键词: 急性呼吸窘迫综合征, 间充质干细胞, 免疫反应

Abstract: Acute respiratory distress syndrome(ARDS)causes respiratory failure, which is associated with severe inflammation and lung damage and has a high mortality and for which there is no therapy. Mesenchymal stem cells(MSCs)are adult multi-progenitor cells that can modulate the immune response and enhance repair of damaged tissue and thus may provide a therapeutic option for ARDS. MSCs demonstrate efficacy in diverse models of in vivo ARDS, decrease bacterial pneumonia and ischemia-reperfusion-induced injury while enhancing repair following ventilator-induced lung injury. MSCs reduce the pro-inflammatory response to injury while augmenting the host response to bacterial infection. MSCs appear to exert their effects via multiple mechanisms—some are cell interaction dependent whereas others are paracrine dependent resulting from both soluble secreted products and microvesicles derived from the cells. Strategies to further enhance the efficacy of MSCs, such as by overexpressing anti-inflammatory or pro-repair molecules, are also being investigated. Encouragingly, early phase clinical trials of MSCs in patients with ARDS are under way, and experience with these cells in trials suggests that the cells are well tolerated. Although considerable translational challenges, such as concerns regarding cell manufacture scale-up and issues regarding cell potency and batch variability, must be overcome, MSCs constitute a highly promising potential therapy for ARDS.

Key words: acute respiratory distress syndrome, mesenchymal stem cells, immune response

中图分类号:

R563.8

瞿海龙,周英莲,张新欣,彭广军. 间充质干细胞治疗ARDS的新观点[J]. 医学研究与教育, 2018, 35(5): 7-11.

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