研究动态
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诱导多能干细胞通过体外表达IGF相关因子和IL-10的免疫调节作用。

Immunomodulatory effects of the induced pluripotent stem cells through expressing IGF-related factors and IL-10 in vitro.

发表日期:2024
作者: Paria Bayati, Marjan Taherian, Nazanin Mojtabavi
来源: CYTOKINE & GROWTH FACTOR REVIEWS

摘要:

诱导多能干细胞(IPSC)代表了解决挑战性疾病(包括各种风湿病)的创新策略。除了再生能力之外,一些研究还表明这些细胞在调节炎症反应方面的潜力。它们发挥作用的潜在机制尚未完全理解。因此,我们的目的是探索与 IGF 途径以及已知具有免疫调节作用的 IL-10 和 TGF-β 相关的基因表达。使用 C57/Bl6 怀孕小鼠来获得小鼠胚胎成纤维细胞 (MEF),然后使用表达多能性基因(OCT4、SOX2、KLF1 和 c-MYC)的慢病毒载体诱导 IPSC。细胞在高糖加白血病抑制因子的DMEM中培养72小时;使用 Igf1、Igf2、Igfbp3、Igfbp4、Irs1、Il-10 和 Tgf-β 基因的特异性引物以及 SYBR green qPCR 主混合物评估基因表达。数据采用2-ΔΔCT法进行分析,并采用t检验进行比较;使用 GraphPad PRISM 软件绘制结果。 MEFs 用作对照。基因表达分析显示,Igf-1、Igf-bp3、Igf-bp4 和 Il-10 显着过表达 (p ≤ .01),而 Igf-2 和 Tgf-b 基因显着下调。 IPSC 裂解物与对照 MEF 的比较。 Irs1 基因表达没有显着改变。IPSC 可能能够通过表达 IGF 信号传导的各种抗炎介质以及 IL-10 来调节炎症反应。这一发现揭示了 IPSC 治疗作用以前未知的方面,可能导致更先进的体内研究和后续临床试验。
Induced Pluripotent Stem Cells (IPSCs) represent an innovative strategy for addressing challenging diseases, including various rheumatologic conditions. Aside from their regenerative capacities, some studies have shown the potential of these cells in the modulation of inflammatory responses. The underlying mechanisms by which they exert their effects have yet to be fully comprehended. Therefore, we aimed to explore the gene expression linked to the IGF pathway as well as IL-10 and TGF-β, which are known to exert immunomodulatory effects.A C57/Bl6 pregnant mouse was used for obtaining mouse embryonic fibroblasts (MEFs), then the IPSCs were induced using lentiviral vectors expressing the pluripotency genes (OCT4, SOX2, KLF1, and c-MYC). Cells were cultured for 72 h in DMEM high glucose plus leukemia inhibitory factor; Evaluating the gene expression was conducted using specific primers for Igf1, Igf2, Igfbp3, Igfbp4, Irs1, Il-10, and Tgf-β genes, as well as SYBR green qPCR master mix. The data were analyzed using the 2-ΔΔCT method and were compared by employing the t test; the results were plotted using GraphPad PRISM software. MEFs were utilized as controls.Gene expression analyses revealed that Igf-1, Igf-bp3, Igf-bp4, and Il-10 were significantly overexpressed (p ≤ .01), while Igf-2 and Tgf-b genes were significantly downregulated in the lysates from IPSCs in comparison with the control MEFs. The Irs1 gene expression was not altered significantly.IPSCs are potentially capable of modulating inflammatory responses through the expression of various anti-inflammatory mediators from the IGF signaling, as well as IL-10. This discovery uncovers a previously unknown dimension of IPSCs' therapeutic effects, potentially leading to more advanced in vivo research and subsequent clinical trials.