Ho Mirabelle S H, Mei Shirley H J, Stewart Duncan J
Sinclair Centre for Regenerative Medicine, Ottawa Hospital Research Institute, Ottawa, Ontario.
Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario.
J Cell Physiol. 2015 Nov;230(11):2606-17. doi: 10.1002/jcp.25028.
It is increasingly recognized that immunomodulation represents an important mechanism underlying the benefits of many stem cell therapies, rather than the classical paradigm of transdifferentiation and cell replacement. In the former paradigm, the beneficial effects of cell therapy result from paracrine mechanism(s) and/or cell-cell interaction as opposed to direct engraftment and repair of diseased tissue and/or dysfunctional organs. Depending on the cell type used, components of the secretome, including microRNA (miRNA) and extracellular vesicles, may be able to either activate or suppress the immune system even without direct immune cell contact. Mesenchymal stromal cells (MSCs), also referred to as mesenchymal stem cells, are found not only in the bone marrow, but also in a wide variety of organs and tissues. In addition to any direct stem cell activities, MSCs were the first stem cells recognized to modulate immune response, and therefore they will be the focus of this review. Specifically, MSCs appear to be able to effectively attenuate acute and protracted inflammation via interactions with components of both innate and adaptive immune systems. To date, this capacity has been exploited in a large number of preclinical studies and MSC immunomodulatory therapy has been attempted with various degrees of success in a relatively large number of clinical trials. Here, we will explore the various mechanism employed by MSCs to effect immunosuppression as well as review the current status of its use to treat excessive inflammation in the context of acute lung injury (ALI) and sepsis in both preclinical and clinical settings.
人们越来越认识到，免疫调节是许多干细胞疗法产生益处的重要机制，而非传统的转分化和细胞替代模式。在前一种模式中，细胞疗法的有益效果源于旁分泌机制和/或细胞间相互作用，而非直接植入并修复患病组织和/或功能失调的器官。根据所使用的细胞类型，分泌组的成分，包括微小RNA（miRNA）和细胞外囊泡，即使在没有直接免疫细胞接触的情况下，也可能激活或抑制免疫系统。间充质基质细胞（MSC），也被称为间充质干细胞，不仅存在于骨髓中，还存在于多种器官和组织中。除了任何直接的干细胞活性外，MSC是最早被认识到可调节免疫反应的干细胞，因此它们将成为本综述的重点。具体而言，MSC似乎能够通过与固有免疫系统和适应性免疫系统的成分相互作用，有效减轻急性和持续性炎症。迄今为止，这种能力已在大量临床前研究中得到利用，并且在相当数量的临床试验中，MSC免疫调节疗法已取得了不同程度的成功。在此，我们将探讨MSC用于实现免疫抑制的各种机制，并回顾其在临床前和临床环境中用于治疗急性肺损伤（ALI）和脓毒症时过度炎症的应用现状。
