Department of Transplant Surgery, Faculty of Medicine, Imperial College London, London SW7 2AZ, UK.
Int J Mol Sci. 2021 Jan 25;22(3):1181. doi: 10.3390/ijms22031181.
Mesenchymal Stromal Cells (MSC) have been shown to exhibit immuno-modulatory and regenerative properties at sites of inflammation. In solid organ transplantation (SOT), administration of MSCs might lead to an alleviation of ischemia-reperfusion injury and a reduction of rejection episodes. Previous reports have suggested 'MSC-preconditioning' of macrophages to be partly responsible for the beneficial effects. Whether this results from direct cell-cell interactions (e.g., MSC trans-differentiation at sites of damage), or from paracrine mechanisms, remains unclear. Immunosuppressive capacities of MSCs from donors of different age and from genetically modified donor animals, often used for in-vivo experiments, have so far not been investigated. We conducted an in vitro study to compare paracrine effects of supernatants from MSCs extracted from young and old wild-type rats (), as well as young and old donor rats positive for the expression of green fluorescent protein , on bone marrow derived macrophages (BMDM). Expression levels of (), (), () and () in BMDMs after treatment with different MSC supernatants were compared by performance of quantitative PCR. We observed different expression patterns of inflammatory markers within BMDMs, depending on age and genotype of origin for MSC supernatants. This must be taken into consideration for preclinical and clinical studies, for which MSCs will be used to treat transplant patients, aiming to mitigate inflammatory and allo-responses.
间充质基质细胞（MSC）已被证明在炎症部位具有免疫调节和再生特性。在实体器官移植（SOT）中，给予 MSC 可能导致减轻缺血再灌注损伤和减少排斥反应发作。先前的报告表明，巨噬细胞的“MSC 预处理”部分负责这些有益作用。这是否来自直接的细胞-细胞相互作用（例如，在损伤部位 MSC 的转分化），还是来自旁分泌机制，目前尚不清楚。来自不同年龄的供体和来自遗传修饰供体动物的 MSC 的免疫抑制能力，通常用于体内实验，迄今为止尚未被研究。我们进行了一项体外研究，比较了从年轻和老年野生型大鼠（）中提取的 MSC 的上清液的旁分泌效应，以及表达绿色荧光蛋白的年轻和老年 供体大鼠的上清液对骨髓来源的巨噬细胞（BMDM）的影响。通过定量 PCR 比较用不同 MSC 上清液处理后的 BMDM 中 （）、 （）、 （）和 （）的表达水平。我们观察到 BMDM 中炎症标志物的表达模式因 MSC 上清液的年龄和基因型而异。这必须在临床前和临床研究中考虑到，这些研究将使用 MSC 来治疗移植患者，旨在减轻炎症和同种反应。
