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灌注流增强 3D 培养乳腺癌细胞的活力和迁移表型。

Perfusion Flow Enhances Viability and Migratory Phenotype in 3D-Cultured Breast Cancer Cells.

机构信息

Laboratory of Cellular and Molecular Engineering "Silvio Cavalcanti", Department of Electrical, Electronic and Information Engineering "G. Marconi" (DEI), Alma Mater Studiorum - University of Bologna, Cesena, FC, Italy.

Osteoncology and Rare Tumors Center, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.

出版信息

Ann Biomed Eng. 2021 Sep;49(9):2103-2113. doi: 10.1007/s10439-021-02727-w. Epub 2021 Feb 4.

Abstract

Conventional 2D cell culture, a traditional tool in pre-clinical studies, can hardly be regarded as a representation of a natural cell microenvironment. In this respect, it might result in altered cellular behaviors. To overcome such a limitation, different approaches have been tested to conduct more representative in vitro studies. In particular, the use of 3D cell culture introduces variables, such as cell-cell and cell-extracellular matrix interactions; cell features such as survival, proliferation and migration are consequently influenced. For an example, an enhanced drug resistance and increased invasiveness are shown by cancer cells when cultured in 3D versus 2D conventional culture models. In this setting however, non-uniform cell distribution and biological behaviors appear throughout the scaffold, due to reduced diffusion of oxygen and nutrients. Perfusion in bioreactor systems can be used to improve medium transport. In this line of reasoning, this study proposes a breast cancer cell culture model sustained by an integrated approach that couples a 3D environment and a fluid perfusion. This model improves viability and uniformness of cell distribution, while inducing morphological, functional and molecular cancer cell remodeling.

摘要

传统的二维细胞培养是临床前研究中的一种传统工具,很难被视为对天然细胞微环境的代表性模拟。在这方面,它可能会导致细胞行为的改变。为了克服这种局限性,已经测试了不同的方法来进行更具代表性的体外研究。特别是,使用三维细胞培养引入了变量,如细胞-细胞和细胞-细胞外基质的相互作用;细胞的特征,如存活、增殖和迁移,因此受到影响。例如,当癌细胞在三维与二维传统培养模型中培养时,其表现出增强的耐药性和侵袭性。然而,在这种情况下,由于氧气和营养物质的扩散减少,支架内的细胞分布和生物学行为变得不均匀。生物反应器系统中的灌注可用于改善培养基的传输。基于这一思路,本研究提出了一种乳腺癌细胞培养模型,该模型采用了一种集成方法,将三维环境和流体灌注结合起来。该模型提高了细胞活力和分布的均匀性,同时诱导了形态、功能和分子水平的癌细胞重塑。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94c5/8455496/c0f7e2ff2b19/10439_2021_2727_Fig1_HTML.jpg

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