Activated and Naïve Allogenic Human Placental Mesenchymal Stromal Cells Exert an Immunomodulatory Effect on Hidradenitis Suppurativa Patient Peripheral Blood Mononuclear Cells.

IF 1.9 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Journal of Interferon and Cytokine Research Pub Date : 2024-07-01 Epub Date: 2024-04-12 DOI:10.1089/jir.2024.0035
Vaiva Jariene, Paulius Valiukevicius, Justinas Maciulaitis, Ugne Kuzaityte, Ruta Insodaite, Ieva Ciapiene, Romaldas Maciulaitis, Skaidra Valiukeviciene
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Abstract

This pilot study aimed to evaluate the immunomodulatory effect of placental mesenchymal stem/stromal cells (MSCs) on peripheral blood mononuclear cells (PBMCs) from patients with hidradenitis suppurativa (HS). Blood samples were collected from 3 healthy and 3 patients with HS. Isolated PBMCs were stained with carboxyfluorescein succinimidyl ester (CFSE) and stimulated with phorbol 12-myristate 13-acetate (PMA)/Ionomycin solution. The PBMCs of patients with HS were co-cultured with naïve MSCs (n-MSCs), activated with tumor necrosis factor (TNF)-α (10 ng/mL) and interferon (IFN)-γ (10 ng/mL) MSCs (a-MSCs), or adalimumab (30 μg/mL). The division index (proliferation inhibition) of PBMCs was analyzed by flow cytometry using the Proliferation Modeling tool after 5 days of coculture. The relative inflammatory gene expression dynamics and cytokine secretion were quantified in triplicate using real-time polymerase chain reaction (PCR) and Luminex assays. PBMCs from the HS control group showed statistically significant increases in interleukin (IL)-6 and IFN-γ cytokine concentrations and IL-17A gene expression when compared with healthy subjects. Statistically significant reduction of the division index was found in the a-MSCs group (P = 0.04). Also, the Luminex assay revealed significantly reduced proinflammatory cytokine concentrations of IL-9 (P = 0.022) and IL-17A (P = 0.022) in the a-MSCs group with the same trend of numerical lowering in n-MSCs group when compared to HS control. The results of real-time PCR revealed a numerical increase in the expression of the IL-1β, IL-36α, and TNF-α genes in both the a-MSCs and n-MSCs groups compared with the HS control. In conclusion, our findings suggest that MSCs can effectively curb PBMCs proliferation and suppress the production of inflammatory cytokines. Moreover, the preactivation of MSCs with IFN-γ and TNF-α before use can enhance their therapeutic effectiveness. Nevertheless, a larger sample size is imperative to validate these results.

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活化和新生的异源人胎盘间充质基质细胞对扁平苔藓患者外周血单核细胞有免疫调节作用
这项试验性研究旨在评估胎盘间充质干/基质细胞(MSCs)对化脓性扁桃体炎(HS)患者外周血单核细胞(PBMCs)的免疫调节作用。采集了3名健康人和3名化脓性扁桃体炎患者的血液样本。分离出的 PBMC 用羧基荧光素琥珀酰亚胺酯(CFSE)染色,并用 12-肉豆蔻酸 13-醋酸酯(PMA)/异诺米霉素溶液刺激。将 HS 患者的 PBMC 与天真间充质干细胞(n-MSCs)、用肿瘤坏死因子(TNF)-α(10 ng/mL)和干扰素(IFN)-γ(10 ng/mL)激活的间充质干细胞(a-MSCs)或阿达木单抗(30 μg/mL)共培养。共培养 5 天后,使用增殖模型工具通过流式细胞仪分析 PBMC 的分裂指数(增殖抑制)。使用实时聚合酶链反应(PCR)和 Luminex 检测法对一式三份的相对炎症基因表达动态和细胞因子分泌进行量化。与健康受试者相比,HS 对照组的白细胞介素(IL)-6 和 IFN-γ 细胞因子浓度以及 IL-17A 基因表达均有统计学意义的显著增加。经统计发现,a-间充质干细胞组的分裂指数明显下降(P = 0.04)。此外,Luminex 检测显示,与 HS 对照组相比,a-间充质干细胞组的促炎细胞因子 IL-9 浓度(P = 0.022)和 IL-17A 浓度(P = 0.022)明显降低,n-间充质干细胞组的数值降低趋势相同。实时 PCR 结果显示,与 HS 对照组相比,a-间充质干细胞组和 n-间充质干细胞组中 IL-1β、IL-36α 和 TNF-α 基因的表达量均有增加。总之,我们的研究结果表明,间充质干细胞能有效抑制 PBMC 的增殖并抑制炎症细胞因子的产生。此外,使用前用 IFN-γ 和 TNF-α 预激活间充质干细胞可提高其治疗效果。不过,要验证这些结果,还需要更大的样本量。
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来源期刊
CiteScore
3.80
自引率
0.00%
发文量
78
审稿时长
2.2 months
期刊介绍: Journal of Interferon & Cytokine Research (JICR) provides the latest groundbreaking research on all aspects of IFNs and cytokines. The Journal delivers current findings on emerging topics in this niche community, including the role of IFNs in the therapy of diseases such as multiple sclerosis, the understanding of the third class of IFNs, and the identification and function of IFN-inducible genes.
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