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Comparative Analysis of the Biosimilar and Innovative G-CSF Modulated Pathways on Umbilical Cord Blood–Derived Mononuclear Cells

机译:生物仿制性和创新的G-CSF调制途径对脐带血血液衍生单核细胞的比较分析

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Biosimilars of granulocyte colony-stimulating factor (G-CSF) have been routinely introduced into clinical practice. However, not functional genomics characterization has been performed yet in comparison with the innovator G-CSF. This study aimed to evaluate the transcriptomic changes in an in vitro model of umbilical cord blood cells (UBC) exposed to G-CSF for the identification of their modulated pathways. Umbilical cord blood cells–derived mononuclear cells (MNCs) were treated with biosimilar and innovator G-CSF for further gene expression profiling analysis using a microarray-based platform. Comparative analysis of biosimilar and innovator G-CSF gene expression signatures allowed us to identify the most commonly modulated pathways by both drugs. In brief, we observed predominantly upmodulation of transcripts related to PI3K-Akt, NF-kappaB, and tumor necrosis factor (TNF) signaling pathways as well as transcripts related to negative regulation of apoptotic process among others. In addition, hematopoietic colony-forming cell assays corroborate the G-CSF phenotypic effects over UBC-derived MNCs. In conclusion, our study suggests that G-CSF impacts UBC-derived cells through the modulation of several signaling pathways associated with cell survival, migration, and proliferation. The concordance observed between biosimilar and innovator G-CSF emphasizes their similarity in regards to their specificity and biological responses.
机译:颗粒细胞菌落刺激因子(G-CSF)的生物纤米已经常规地引入临床实践中。然而,与创新者G-CSF相比,尚未进行功能基因组学表征。该研究旨在评估暴露于G-CSF的脐带血细胞(UBC)的体外模型中的转录组变化,以鉴定其调节途径。使用微阵列的平台,用生物仿制剂和创新的G-CSF治疗脐带血细胞衍生的单核细胞(MNC),用于进一步的基因表达分析分析。生物仿制性和创新者G-CSF基因表达签名的比较分析使我们能够识别两种药物最常见的途径。简而言之,我们观察到与PI3K-AKT,NF-κB和肿瘤坏死因子(TNF)信号传导途径(TNF)信号传导途径(TNF)信号传导途径以及与凋亡过程中的阴性调节相关的转录物中的转录物。此外,造血菌落形成细胞测定证实了通过UBC衍生的MNC对G-CSF表型作用进行了证实。总之,我们的研究表明,G-CSF通过调节与细胞存活,迁移和增殖相关的几种信号通路来影响UBC衍生细胞。 BioSimilar和Innovator G-CSF之间观察到的一致性强调了他们对其特异性和生物反应的相似性。

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