Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Eur Cytokine Netw. 2022 Sep 1;33(3):70-78. doi: 10.1684/ecn.2022.0482.
Although mesenchymal stem cells (MSCs) have exhibited promising immunomodulatory potential in preclinical studies, clinical studies have revealed variable results. These results often depend on environmental cues. Pre-conditioning MSCs with cytokines is one of the methods used to enhance their immunomodulatory effects. In this study, we harvested adipose-derived MSCs from mice and cultured them with different doses of the cytokine, IFN-γ, and the corticosteroid drug, dexamethasone, in order to investigate their effects on MSC immunosuppressive function. We found the co-culture or supernatant of MSCs, pre-conditioned with IFN-γ, together with spleen mononuclear cells resulted in a significant reduction of mononuclear cell proliferation. Although the supernatant of MSCs, pre-conditioned with dexamethasone, showed similar results, dexamethasone pre-conditioning of co-cultured MSCs increased mononuclear cell proliferation. The results further our understanding of immune-related effects of MSCs which may provide a basis for further in vivo studies to achieve better clinical results. We propose that pre-conditioning with cytokines might be an effective method to boost the immunomodulatory effects of MSCs.
虽然间充质干细胞(MSCs)在临床前研究中表现出了有希望的免疫调节潜力,但临床研究却揭示了不同的结果。这些结果往往取决于环境线索。用细胞因子对 MSCs 进行预处理是增强其免疫调节作用的方法之一。在这项研究中,我们从小鼠中收获脂肪来源的 MSCs,并在不同剂量的细胞因子 IFN-γ和皮质类固醇药物地塞米松的作用下培养它们,以研究它们对 MSC 免疫抑制功能的影响。我们发现,与 IFN-γ预处理的 MSC 共培养物或上清液一起孵育的脾单核细胞,导致单核细胞增殖显著减少。尽管用地塞米松预处理的 MSC 上清液显示出类似的结果,但共培养物中地塞米松预处理的 MSC 增加了单核细胞的增殖。这些结果进一步了解了 MSC 的免疫相关影响,这可能为进一步的体内研究提供了基础,以获得更好的临床结果。我们提出,用细胞因子预处理可能是增强 MSCs 免疫调节作用的有效方法。