Stem Cell Research Centre, Government Stanley Hospital, Chennai, India.
Stem Cell and Molecular Biology Lab, Department of Biotechnology, Indian Institute of Technology Madras, Chennai, India.
Cytotherapy. 2022 Feb;24(2):110-123. doi: 10.1016/j.jcyt.2021.09.005. Epub 2021 Nov 2.
Mesenchymal stromal cells (MSCs) are very advantageous in the field of regenerative medicine because of their immunomodulatory properties. However, reports show that these properties vary from source to source. Hence, understanding the source-dependent specificity of MSCs and their immunomodulatory abilities will enable optimal use of MSCs in cell-based therapies. Here, we studied human MSCs from three different sources, adipose tissue (AT), bone marrow (BM) and Wharton's jelly (WJ), with respect to phenotypic responses of human peripheral blood mononuclear immune cells (hPBMCs/MNCs) and the concurrent changes in cytokine expression in MSCs, under mitogen-stimulated co-culture conditions. We used cytometric analysis to study the immunoregulatory properties of MSCs on MNCs and cytokine profiling of MSCs using a customized PCR array and solid-phase sandwich enzyme-linked immunosorbent assay. Our results reveal differential modulation of immune cells as well as MSCs upon activation by the mitogen phytohemagglutinin, independently and in co-culture. Notably, we observed source-specific MSC-cytokine signatures under stimulated conditions. Our results show that AT-MSCs up-regulate VEGF, BM-MSCs up-regulate PTGS-2 and WJ-MSCs increase expression of IDO considerably compared with controls. This remarkable modulation in source-specific cytokine expression was also validated at a functional level by quantitative protein expression studies. In our hands, even though MSCs from AT, BM and WJ sources exhibit characteristic immunomodulatory properties, our results highlight that MSCs sourced from different tissues may exhibit unique cytokine signatures and thus may be suitable for specific regenerative applications.
间充质基质细胞（MSCs）因其免疫调节特性在再生医学领域非常有优势。然而，报告显示这些特性因来源而异。因此，了解 MSCs 的来源依赖性特异性及其免疫调节能力将使 MSC 能够在基于细胞的治疗中得到最佳利用。在这里，我们研究了来自三个不同来源的人 MSCs，即脂肪组织（AT）、骨髓（BM）和 Wharton 胶（WJ），在有丝分裂原刺激的共培养条件下，研究了人外周血单核免疫细胞（hPBMCs/MNCs）的表型反应以及 MSC 中细胞因子表达的同时变化。我们使用细胞计量分析来研究 MSC 对 MNCs 的免疫调节特性，并使用定制的 PCR 阵列和固相夹心酶联免疫吸附测定法对 MSC 的细胞因子谱进行分析。我们的结果表明，在有丝分裂原植物血凝素的刺激下，免疫细胞和 MSC 会发生不同的调节，无论是独立培养还是共培养。值得注意的是，我们观察到在刺激条件下 MSC-细胞因子特征具有来源特异性。我们的结果表明，与对照组相比，AT-MSCs 上调了 VEGF，BM-MSCs 上调了 PTGS-2，而 WJ-MSCs 则显著增加了 IDO 的表达。这种来源特异性细胞因子表达的显著调节在功能水平上也通过定量蛋白表达研究得到了验证。在我们的研究中，尽管来自 AT、BM 和 WJ 来源的 MSC 表现出特征性的免疫调节特性，但我们的结果强调，来自不同组织的 MSC 可能具有独特的细胞因子特征，因此可能适合特定的再生应用。
