Department of Environmental Medicine, Cooperative Medicine Unit, Research and Education Faculty, Medicine Science Cluster, Kochi Medical School (KMS), Kochi University, Kohasu, Oko-Cho, Nankoku City, Kochi Prefecture, 783-8505, Japan.
CEA-Université Paris Sud INSERM U1184, IDMIT Department, IBFJ, DRF, Fontenay-aux-Roses, France.
Stem Cell Res Ther. 2019 Feb 13;10(1):56. doi: 10.1186/s13287-019-1158-4.
Mesenchymal stem/stromal cells (MSCs) delivered as cell therapy to individuals with degenerative and/or inflammatory disorders can help improve organ features and resolve inflammation, as demonstrated in preclinical studies and to some extent in clinical studies. MSCs have trophic, homing/migration, and immunosuppression functions, with many benefits in therapeutics. MSC functions are thought to depend on the paracrine action of soluble factors and/or the expression of membrane-bound molecules, mostly belonging to the molecular class of adhesion molecules, chemokines, enzymes, growth factors, and interleukins. Cutting-edge studies underline bioactive exchanges, including that of ions, nucleic acids, proteins, and organelles transferred from MSCs to stressed cells, thereby improving the cells' survival and function. From this aspect, MSC death modulation function appears as a decisive biological function that could carry a significant part of the therapeutic effects of MSCs. Identifying the function and modes of actions of MSCs in modulating cell death may be exploited to enhance consistency and efficiency of cell therapy that is based on MSCs as medical treatment for degenerative and/or inflammatory diseases. Here, we review the essentials of MSC functions in modulating cell death in unfit cells, and its modes of actions based on current advances and outline the clinical implications.
间充质干细胞（MSCs）作为细胞疗法输送给退行性和/或炎症性疾病患者，有助于改善器官功能并缓解炎症，这已在临床前研究中得到证实，在一定程度上也在临床研究中得到证实。MSCs 具有营养、归巢/迁移和免疫抑制功能，在治疗中有许多益处。MSCs 的功能被认为取决于可溶性因子的旁分泌作用和/或膜结合分子的表达，这些分子主要属于黏附分子、趋化因子、酶、生长因子和白细胞介素的分子类别。最新研究强调了生物活性的交换，包括从 MSCs 转移到应激细胞的离子、核酸、蛋白质和细胞器的交换，从而提高细胞的存活和功能。从这个角度来看，MSC 死亡调节功能似乎是一种决定性的生物学功能，可能承载着 MSC 治疗退行性和/或炎症性疾病的大部分治疗效果。确定 MSCs 调节细胞死亡的功能和作用方式，可能有助于提高基于 MSCs 的细胞治疗的一致性和效率，作为退行性和/或炎症性疾病的治疗方法。在这里，我们回顾了 MSCs 在调节不适宜细胞的细胞死亡方面的功能要点及其作用方式，并根据最新进展概述了其临床意义。
