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首页> 外文期刊>Materials science & engineering >Comparison of 2D and 3D cell culture models for cell growth, gene expression and drug resistance
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Comparison of 2D and 3D cell culture models for cell growth, gene expression and drug resistance

机译：比较2D和3D细胞培养模型的细胞生长，基因表达和耐药性

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In vitro drug screening is widely used in the development of new drugs, because they constitute a cost-effective approach to select compounds with more potential for therapy. They are also an attractive alternative to in vivo testing. However, most of these assays are done in two-dimensional culture models, where cells are grown on a polystyrene or glass flat surface. In order to develop in vitro models that would more closely resemble physiological conditions, three-dimensional models have been developed. Here, we introduce two novel fully synthetic scaffolds produced using the polymer polyhydroxybutyrate (PHB): a Solvent-Casting Particle-Leaching (SCPL) membrane; and an electrospun membrane, to be used for 3D cultures of B16 F10 murine melanoma cells and 4T1 murine breast cancer cells. A 2D cell culture system in regular tissue culture plates and a classical 3D model where cells are grown on a commercially available gel derived from Engelbreth-Holm Swarm (EHS) tumor were used for comparison with the synthetic scaffolds. Cells were also collected from in vivo tumors grown as grafts in syngeneic mice. Morphology, cell viability, response to chemotherapy and gene expression analysis were used to compare all systems. In the electrospun membrane model, cells were grown on nanometer-scale fibers and in the SCPL membrane, which provides a foam-like structure for cell growth, pore sizes varied. Cells grown on all 3D models were able to form aggregates and spheroids, allowing for increased cell-cell contact when compared with the 2D system. Cell morphology was also more similar between 3D systems and cells collected from the in vivo tumors. Cells grown in 3D models showed an increase in resistance to dacarbazine, and cisplatin. Gene expression analysis also revealed similarities among all 3D platforms. The similarities between the two synthetic systems to the classic EHS gel model highlight their potential application as cost effective substitutes in drug screening, in which fully synthetic models could represent a step towards higher reproducibility. We conclude PHB synthetic membranes offer a valuable alternative for 3D cultures.
机译：体外药物筛选在新药开发中被广泛使用，因为它们构成了一种具有成本效益的方法来选择具有更大治疗潜力的化合物。它们还是体内测试的一种有吸引力的替代方法。但是，大多数这些测定都是在二维培养模型中完成的，其中细胞在聚苯乙烯或玻璃平坦表面上生长。为了建立更类似于生理条件的体外模型，已经开发了三维模型。在这里，我们介绍两种使用聚合物聚羟基丁酸酯（PHB）生产的新型完全合成支架：一种溶剂铸造颗粒浸出（SCPL）膜；以及电纺膜，用于B16 F10鼠黑色素瘤细胞和4T1鼠乳腺癌细胞的3D培养。使用常规组织培养板中的2D细胞培养系统和经典3D模型（其中细胞在可从Engelbreth-Holm Swarm（EHS）肿瘤衍生的市售凝胶上生长）与合成支架进行比较。还从在同系小鼠中作为移植物生长的体内肿瘤中收集细胞。使用形态学，细胞活力，对化学疗法的反应和基因表达分析来比较所有系统。在电纺膜模型中，细胞在纳米级纤维上和SCPL膜中生长，SCPL膜为细胞生长提供了类似泡沫的结构，孔径变化。在所有3D模型上生长的细胞都能够形成聚集体和球体，与2D系统相比，可以增加细胞间的接触。 3D系统与从体内肿瘤收集的细胞之间的细胞形态也更加相似。在3D模型中生长的细胞显示出对达卡巴嗪和顺铂的抗性增加。基因表达分析还揭示了所有3D平台之间的相似性。两种合成系统与经典EHS凝胶模型之间的相似之处突显了它们在药物筛选中作为具有成本效益的替代品的潜在应用，其中完全合成的模型可能代表了向更高重现性迈出的一步。我们得出结论，PHB合成膜为3D培养提供了有价值的替代方法。

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  • 来源
    《Materials science & engineering》 |2020年第2期|110264.1-110264.10|共10页
  • 作者

    Fontoura Julia C.; Viezzer Christian; dos Santos Fabiana G.; Ligabue Rosane A.; Weinlich Ricardo; Puga Renato D.; Antonow Dyeison; Severino Patricia; Bonorino Cristina;

  • 作者单位

    Pontiftcia Univ Catolica Rio Grande Sul PUCRS Lab Imunol Celular & Mol Porto Alegre RS Brazil|Univ Fed Ciencias Saude Dept Ciencias Basicas Saude Porto Alegre RS Brazil;

    Pontiftcia Univ Catolica Rio Grande Sul PUCRS Lab Imunol Celular & Mol Porto Alegre RS Brazil;

    Pontificia Univ Catolica Rio Grande do Sul Lab Caracterizacao Mat Porto Alegre RS Brazil;

    Hosp Israelita Albert Einstein Sao Paulo SP Brazil;

    Pontificia Univ Catolica Rio Grande do Sul Tecnopuc Inst Petr & Nat Resources IPR Porto Alegre RS Brazil;

    Univ Fed Ciencias Saude Dept Ciencias Basicas Saude Porto Alegre RS Brazil|Univ Calif San Diego Sch Med Dept Surg La Jolla CA 92093 USA;

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