Carrara Stefania C, Davila-Lezama Amanda, Cabriel Clément, Berenschot Erwin J W, Krol Silke, Gardeniers J G E, Izeddin Ignacio, Kolmar Harald, Susarrey-Arce Arturo
Institute for Organic Chemistry and Biochemistry, Technical University of Darmstadt, Alarich-Weiss-Strasse 4, D-64287 Darmstadt, Germany.
Centre for Synthetic Biology, Technische Universität Darmstadt, Darmstadt, Germany.
Mater Today Bio. 2023 Dec 6;24:100897. doi: 10.1016/j.mtbio.2023.100897. eCollection 2024 Feb.
cellular models denote a crucial part of drug discovery programs as they aid in identifying successful drug candidates based on their initial efficacy and potency. While tremendous headway has been achieved in improving 2D and 3D culture techniques, there is still a need for physiologically relevant systems that can mimic or alter cellular responses without the addition of external biochemical stimuli. A way forward to alter cellular responses is using physical cues, like 3D topographical inorganic substrates, to differentiate macrophage-like cells. Herein, protein secretion and gene expression markers for various macrophage subsets cultivated on a 3D topographical substrate are investigated. The results show that macrophages differentiate into anti-inflammatory M2-type macrophages, secreting increased IL-10 levels compared to the controls. Remarkably, these macrophage cells are differentiated into the M2d subset, making up the main component of tumour-associated macrophages (TAMs), as measured by upregulated and mRNA. M2d subset differentiation is attributed to the topographical substrates with 3D fractal-like geometries arrayed over the surface, else primarily achieved by tumour-associated factors . From a broad perspective, this work paves the way for implementing 3D topographical inorganic surfaces for drug discovery programs, harnessing the advantages of assays without external stimulation and allowing the rapid characterisation of therapeutic modalities in physiologically relevant environments.
细胞模型是药物发现计划的关键组成部分，因为它们有助于根据药物的初始疗效和效力来确定成功的候选药物。虽然在改进二维和三维培养技术方面已经取得了巨大进展，但仍然需要能够在不添加外部生化刺激的情况下模拟或改变细胞反应的生理相关系统。改变细胞反应的一种方法是使用物理线索，如三维拓扑无机底物，来分化巨噬细胞样细胞。在此，研究了在三维拓扑底物上培养的各种巨噬细胞亚群的蛋白质分泌和基因表达标志物。结果表明，巨噬细胞分化为抗炎性M2型巨噬细胞，与对照组相比，其白细胞介素-10水平升高。值得注意的是，这些巨噬细胞分化为M2d亚群，通过上调的和mRNA测量，M2d亚群构成肿瘤相关巨噬细胞（TAM）的主要成分。M2d亚群的分化归因于表面排列有三维分形样几何形状的拓扑底物，否则主要由肿瘤相关因子实现。从广义上讲，这项工作为在药物发现计划中实施三维拓扑无机表面铺平了道路，利用了无外部刺激检测的优势，并允许在生理相关环境中快速表征治疗方式。
