IFN-γ licensing to mesenchymal stem cells (MSCs) is applied to enhance the therapeutic potential of MSCs. However, although the features of MSCs are affected by several stimuli, little information is available on changes to the therapeutic potential of IFN-γ-licensed differentiated MSCs during xenogeneic applications. Therefore, the present study is aimed at clarifying the effects of adipogenic/osteogenic differentiation and IFN-γ licensing on the in vitro immunomodulatory and migratory properties of porcine bone marrow-derived MSCs in xenogeneic applications using human peripheral blood mononuclear cells (PBMCs). IFN-γ licensing in differentiated MSCs lowered lineage-specific gene expression but did not affect MSC-specific cell surface molecules. Although indoleamine 2,3 deoxygenase (IDO) activity and expression were increased after IFN-γ licensing in undifferentiated MSCs, they were reduced after differentiation. IFN-γ licensing to differentiated MSCs elevated the reduced IDO expression in differentiated MSCs; however, the increase was not sufficient to reach to the level achieved by undifferentiated MSCs. During a mixed lymphocyte reaction with quantification of TNF-α concentration, proliferation and activation of xenogeneic PBMCs were suppressed by undifferentiated MSCs but inhibited to a lesser extent by differentiated MSCs. IFN-γ licensing increasingly suppressed proliferation of PBMCs in undifferentiated MSCs but it was incapable of elevating the reduced immunosuppressive ability of differentiated MSCs. Migratory ability through a scratch assay and gene expression study was reduced in differentiated MSCs than their undifferentiated counterparts; IFN-γ licensing was unable to enhance the reduced migratory ability in differentiated MSCs. Similar results were found in a Transwell system with differentiated MSCs in the upper chamber toward xenogeneic PBMCs in the lower chamber, despite IFN-γ licensing increased the migratory ability of undifferentiated MSCs. Overall, IFN-γ licensing did not enhance the reduced immunomodulatory and migratory properties of differentiated MSCs in a xenogeneic application. This study provides a better understanding of the ways in which MSC therapy can be applied.

中文翻译：

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IFN-γ 许可不会增强体外异种应用中分化诱导的猪骨髓源间充质干细胞的免疫调节潜力和迁移能力降低

间充质干细胞 (MSC) 的IFN- γ许可用于增强 MSC 的治疗潜力。然而，尽管 MSC 的特征受到多种刺激的影响，但关于 IFN- γ许可的分化 MSC 在异种应用期间的治疗潜力变化的信息很少。因此，本研究旨在阐明成脂/成骨分化和 IFN- γ许可对使用人外周血单核细胞 (PBMC) 进行异种应用的猪骨髓源性 MSC 的体外免疫调节和迁移特性的影响。干扰素-γ分化的 MSC 中的许可降低了谱系特异性基因表达，但不影响 MSC 特异性细胞表面分子。尽管在未分化的 MSC 中使用IFN- γ许可后吲哚胺 2,3 脱氧酶 (IDO) 的活性和表达增加，但它们在分化后降低。向分化的 MSC 发放IFN- γ提高了分化的 MSC 中降低的 IDO 表达；然而，这种增加不足以达到未分化 MSC 所达到的水平。在量化 TNF- α浓度的混合淋巴细胞反应期间，异种 PBMC 的增殖和活化被未分化的 MSC 抑制，但被分化的 MSC 在较小程度上抑制。干扰素-γ许可越来越多地抑制未分化 MSC 中 PBMC 的增殖，但无法提高已分化 MSC 降低的免疫抑制能力。通过划痕分析和基因表达研究，分化的 MSC 比未分化的对应物的迁移能力降低；IFN- γ许可无法增强分化的 MSC 中降低的迁移能力。在 Transwell 系统中发现了类似的结果，尽管 IFN- γ许可增加了未分化 MSC 的迁移能力，但在上腔室中具有分化的 MSCs 朝向下腔室中的异种 PBMC 。总的来说，IFN- γ许可并没有增强异种应用中分化的 MSC 降低的免疫调节和迁移特性。这项研究提供了对 MSC 疗法的应用方式的更好理解。