Molecular Oncology and Angiogenesis Unit, Ospedale Policlinico San Martino, Genoa, Italy.
Division of Immunology, Transplants and Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy.
Curr Stem Cell Res Ther. 2019;14(4):344-350. doi: 10.2174/1574888X14666181205115452.
Mesenchymal stromal cells (MSC) are mesodermal elements characterized by the ability to differentiate into several types of cells present mainly in connective tissues. They play a key function in tissue homeostasis and repair. Furthermore, they exert a strong effect on both innate and adaptive immune response. The main current of thought considers MSC as strong inhibitors of the immune system. Indeed, the first description of MSC immunomodulation pointed out their inability to induce alloimmune responses and their veto effects on mixed lymphocyte reactions. This inhibition appears to be mediated both by direct MSC interaction with immune cells and by soluble factors. Unfortunately, evidence to support this notion comes almost exclusively from in vitro experiments. In complex experimental systems, it has been shown that MSC can exert immunosuppressive effects also in vivo, either in murine models or in transplanted patients to avoid the graft versus host disease. However, it is still debated how the small number of administered MSC can regulate efficiently a large number of host effector lymphocytes. In addition, some reports in the literature indicate that MSC can trigger rather than inhibit lymphocyte activation when a very low number of MSC are co-cultured with lymphocytes. This would imply that the ratio between the number of MSC and immune cells is a key point to forecast whether MSC will inhibit or activate the immune system. Herein, we discuss the conflicting results reported on the immunomodulatory effects of MSC to define which features are relevant to understand their behavior and cross-talk with immune cells.
间充质基质细胞（MSC）是中胚层细胞，其特征是能够分化为主要存在于结缔组织中的几种类型的细胞。它们在组织稳态和修复中发挥着关键作用。此外，它们对先天和适应性免疫反应都有强烈的影响。目前的主流观点认为 MSC 是免疫系统的强大抑制剂。事实上，MSC 免疫调节的第一个描述指出了它们不能诱导同种免疫反应，以及它们对混合淋巴细胞反应的否决效应。这种抑制似乎是通过 MSC 与免疫细胞的直接相互作用和可溶性因子介导的。不幸的是，支持这一观点的证据几乎完全来自体外实验。在复杂的实验系统中，已经表明 MSC 也可以在体内发挥免疫抑制作用，无论是在小鼠模型中还是在移植患者中，以避免移植物抗宿主病。然而，仍然存在争议的是，少量给予的 MSC 如何能够有效地调节大量宿主效应淋巴细胞。此外，文献中的一些报道表明，当非常少量的 MSC 与淋巴细胞共培养时，MSC 可以触发而不是抑制淋巴细胞的激活。这意味着 MSC 与免疫细胞数量之间的比例是预测 MSC 是否会抑制或激活免疫系统的关键。在此，我们讨论了关于 MSC 免疫调节作用的相互矛盾的结果，以确定哪些特征与理解它们与免疫细胞的相互作用有关。
