Macrophage Polarization Profiling in Dynamic Culture System.

IF 5 4区医学 Q3 BIOPHYSICS

Cellular and molecular bioengineering Pub Date : 2025-08-25 eCollection Date: 2025-08-01 DOI:10.1007/s12195-025-00863-0

Alperen Yılmaz, Resul Özbilgiç, Elifsu Polatlı, İbrahim Halilullah Erbay, Duygu Sağ, Sinan Güven

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引用次数: 0

Abstract

Purpose: In this study, we aimed to develop a dynamic on-chip platform to study macrophage polarization in a more physiologically relevant way by incorporating mechanical forces which have been recently shown to play important roles in macrophage biology.

Methods: We developed polymethyl methacrylate (PMMA) based platform. We examined the effects of the dynamic microenvironment on polarization states of human monocyte derived macrophages (HMDMs) towards the M1 and M2a phenotypes using lipopolysaccharide (LPS)/interferon-γ (IFN-γ) and interleukin-4 (IL-4) respectively for both static and dynamic conditions. M1 and M2 polarization levels were assessed by qPCR and flow cytometry analyses.

Results: M1 and M2 polarization was achieved successfully under dynamic and static conditions. Our platform establishes that the mechanotransductive stimulation through shear stress during polarization has direct synergistic effects with stimulants on TNF-α secretion within HMDMs. Exposure to media flow rates of 0.5, 2.5, and 5 µl/min without stimulants is insufficient to induce macrophage polarization.

Conclusion: The dynamic environment present inside our dynamic on-chip culture platform influences the human monocyte-derived macrophages (HMDMs) to become polarized into M1 phenotype at a greater level.

Supplementary information: The online version contains supplementary material available at 10.1007/s12195-025-00863-0.

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动态培养系统中巨噬细胞极化谱。

目的：在本研究中，我们旨在开发一个动态芯片平台，通过结合最近被证明在巨噬细胞生物学中起重要作用的机械力，以更生理学的方式研究巨噬细胞极化。方法：建立基于聚甲基丙烯酸甲酯（PMMA）的平台。我们使用脂多糖(LPS)/干扰素-γ (IFN-γ)和白细胞介素-4 （IL-4）分别在静态和动态条件下研究了动态微环境对人单核细胞来源的巨噬细胞（HMDMs）向M1和M2a表型极化状态的影响。采用qPCR和流式细胞术检测M1和M2极化水平。结果：在动态和静态条件下均成功实现了M1和M2极化。我们的平台证实，极化过程中通过剪切应力产生的机械转导刺激与兴奋剂对HMDMs内TNF-α分泌有直接的协同作用。暴露于0.5、2.5和5µl/min的培养基流速下而不使用刺激物不足以诱导巨噬细胞极化。结论：动态片上培养平台内的动态环境影响人单核细胞源性巨噬细胞（HMDMs）在更大程度上极化为M1表型。补充信息：在线版本包含补充资料，可在10.1007/s12195-025-00863-0获得。

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来源期刊

Cellular and molecular bioengineering 生物-生物物理

CiteScore

5.60

自引率

3.60%

发文量

审稿时长

>12 weeks

期刊介绍： The field of cellular and molecular bioengineering seeks to understand, so that we may ultimately control, the mechanical, chemical, and electrical processes of the cell. A key challenge in improving human health is to understand how cellular behavior arises from molecular-level interactions. CMBE, an official journal of the Biomedical Engineering Society, publishes original research and review papers in the following seven general areas: Molecular: DNA-protein/RNA-protein interactions, protein folding and function, protein-protein and receptor-ligand interactions, lipids, polysaccharides, molecular motors, and the biophysics of macromolecules that function as therapeutics or engineered matrices, for example. Cellular: Studies of how cells sense physicochemical events surrounding and within cells, and how cells transduce these events into biological responses. Specific cell processes of interest include cell growth, differentiation, migration, signal transduction, protein secretion and transport, gene expression and regulation, and cell-matrix interactions. Mechanobiology: The mechanical properties of cells and biomolecules, cellular/molecular force generation and adhesion, the response of cells to their mechanical microenvironment, and mechanotransduction in response to various physical forces such as fluid shear stress. Nanomedicine: The engineering of nanoparticles for advanced drug delivery and molecular imaging applications, with particular focus on the interaction of such particles with living cells. Also, the application of nanostructured materials to control the behavior of cells and biomolecules.