TP53 缺失通过上调 NF-κB-IFN-β-MHC-Ia 信号促进骨肉瘤对 NK 细胞的抵抗
TP53 Loss Elevates NF-κB-IFN-β-MHC-Ia Signaling to Promote NK Cell Resistance in Osteosarcoma.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:A Comparative Study of the Bone Marrow- and Umbilical Cord-Derived Mesenchymal Stem Cells (MSCs) Efficiency on Generating MSC-Educated Macrophages (MEMs).
A Comparative Study of the Bone Marrow- and Umbilical Cord-Derived Mesenchymal Stem Cells (MSCs) Efficiency on Generating MSC-Educated Macrophages (MEMs).
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据我们所知,本研究首次表明,MQs 与 UC 来源的 MSCs 共培养可高效促进 MEMs 的生成,其效果甚至优于 BM-MSCs;这揭示了 UC 作为体外教育 MQs 的替代来源所具有的广阔前景。
首先分离单核细胞并培养5天,获得M0 MQ;随后在直接和间接条件下分别与BM-MSC或UC-MSC共培养。共培养3天后评估MEM特异性表面标志物,以及促炎和抗炎细胞因子基因表达。
与BM和UC来源MSC共培养后,MEM中M2 MQ特异性标志物CD163/CD206表面表达增加,而M1 MQ特异性标志物CD80/CD86未显著变化。与对照MQ相比,UC-MSC共培养后MEM中的PD-L1 mRNA以及IL-6、IL-10和TGF-β等抗炎细胞因子表达增加(p<0.05),IL-12表达则显著降低(p<0.001)。
据我们所知,本研究首次显示,与UC-MSC共培养可有效生成MEM,效果甚至优于BM-MSC;这凸显了UC作为体外教育MQ替代来源的潜力。
Mesenchymal stem cells (MSCs) have gained much more attention in cell therapy and regenerative medicine due to their immunosuppressive effects. MSCs have interaction with other immune cells, such as macrophages (MQs). Bone marrow (BM)-derived MSCs can educate MQs toward MSC-educated MQs (MEMs) which possess an anti-inflammatory immunophenotype. Given this and based on the important limitations of BM collection, we hypothesized whether co-culture of MQs with umbilical cord (UC)-derived MSCs can result in the MEM phenotype.
First, isolated monocytes cultured for five days to obtain M0 MQs. Then, they were co-cultured with either BM- or UC-MSCs under direct and indirect conditions. After three days of co-culture, MEM-specific surface markers, as well as the gene expression of inflammatory and anti-inflammatory cytokines, were evaluated.
Surface expression of CD163/CD206, as specific markers for M2 MQs, increased in MEMs after co-culture with BM- and UC-derived MSCs, while CD80/CD86 expression (specific markers for M1 MQs) didn't change significantly. The mRNA expressions of PDL-1 as well as anti-inflammatory cytokines, including IL-6, IL-10, and TGF also increased in MEMs after co-culture of UC-MSCs compared to control MQs (p <.05), while the expression of IL-12 was significantly decreased (p<.001).
To the best of our knowledge, this study shows for the first time that the co-culture of MQs with UC-derived MSCs efficiently contributes to the generation of MEMs even greater than BM-MSCs; shedding light on the promising potential of UC as an alternative source to educate MQs in vitro.
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