Background

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder associated with several complications. Adipose tissue-derived mesenchymal stem cells (AT-MSCs) represent an emerging type of MSCs with high plasticity and immunoregulatory capabilities and are useful for treating inflammation-related disorders such as T2DM. However, the pathogenic microenvironment of T2DM may affect their therapeutic potential. We aimed to examine the impact of the diabetic milieu on the immunomodulatory/anti-inflammatory potential of AT-MSCs.

Methods

We assessed the proliferation potential, cell surface expression of MSC-characteristic markers and immunomodulatory markers, along with the gene expression and protein secretion of pro-inflammatory and anti-inflammatory cytokines and adipokines in AT-MSCs derived from T2DM patients (dAT-MSCs) vs. those derived from non-diabetic volunteers (ndAT-MSCs). Furthermore, we evaluated the IFN-γ priming effect on both groups.

Results

Our data revealed comparable proliferative activities in both groups. Flow cytometric analysis results showed a lower expression of CD200 and CD276 on dAT-MSCs vs. ndAT-MSCs. qPCR demonstrated upregulation of IL-1β associated with a downregulation of IL-1RN in dAT-MSCs vs. ndAT-MSCs. IFN-γ priming induced an elevation in CD274 expression associated with IDO1 and ILRN overexpression and IL-1β downregulation in both groups. ELISA analysis uncovered elevated levels of secreted IL-1β, TNF, and visfatin/NAMPT in dAT-MSCs, whereas IL-1RA and IDO levels were reduced. ELISA results were also evident in the secretome of dAT-MSCs upon IFN-γ priming.

Conclusions

This study suggests that the T2DM milieu alters the immunomodulatory characteristics of AT-MSCs with a shift towards a proinflammatory phenotype which may restrain their autologous therapeutic use. Furthermore, our findings indicate that IFN-γ priming could be a useful strategy for enhancing dAT-MSC anti-inflammatory potential.

中文翻译：

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2型糖尿病对脂肪组织间充质干细胞免疫调节特性的影响

 背景

2 型糖尿病 (T2DM) 是一种与多种并发症相关的慢性代谢性疾病。脂肪组织源性间充质干细胞 (AT-MSC) 是一种新兴的 MSC 类型，具有高可塑性和免疫调节能力，可用于治疗 T2DM 等炎症相关疾病。然而，T2DM 的致病微环境可能会影响其治疗潜力。我们的目的是研究糖尿病环境对 AT-MSC 的免疫调节/抗炎潜力的影响。

 方法

我们评估了源自 T2DM 患者的 AT-MSC (dAT-MSC) 的增殖潜力、MSC 特征标记和免疫调节标记的细胞表面表达，以及促炎和抗炎细胞因子和脂肪因子的基因表达和蛋白质分泌。与。那些来自非糖尿病志愿者（ndAT-MSC）。此外，我们评估了两组的 IFN-γ 启动效应。

 结果

我们的数据显示两组的增殖活性相当。流式细胞术分析结果显示，与 ndAT-MSC相比， dAT-MSC 上 CD200 和 CD276 的表达较低。 qPCR证明dAT-MSC 中 IL-1β 的上调与 IL-1RN 的下调相关。 ndAT-MSC。 IFN-γ引发诱导两组中与 IDO1 和 ILRN 过表达以及 IL-1β 下调相关的 CD274 表达升高。 ELISA 分析发现 dAT-MSC 中分泌的 IL-1β、TNF 和内脂素/NAMPT 水平升高，而 IL-1RA 和 IDO 水平降低。 IFN-γ 引发后 dAT-MSC 的分泌组中 ELISA 结果也很明显。

 结论

这项研究表明，T2DM 环境改变了 AT-MSC 的免疫调节特性，向促炎表型转变，这可能会限制其自体治疗用途。此外，我们的研究结果表明 IFN-γ 启动可能是增强 dAT-MSC 抗炎潜力的有用策略。