Computational model of the cancer necrotic core formation in a tumor-on-a-chip device

被引:1
|
作者
Bonifacio, Elton Diego [1 ,2 ]
Araujo, Cleudmar Amaral [2 ]
Guimaraes, Marcilia Valeria [3 ]
Souza, Marcio Peres de [2 ]
Lima, Thiago Parente [1 ]
Freitas, Bethania Alves de Avelar [1 ]
Gonzalez-Torres, Libardo Andres [1 ]
机构
[1] Univ Fed Vales Jequitinhonha & Mucuri, Inst Sci & Technol, Diamantina, Brazil
[2] Univ Fed Uberlandia, Brazilian Reference Ctr Assist Technol Innovat CIN, Uberlandia, Brazil
[3] Informat Technol Ctr CTI Renato Archer, Campinas, SP, Brazil
关键词
Tumor cells; Microfluidic devices; Finite element analysis; Necrotic core; CELL-CULTURE; GLUCOSE DIFFUSIVITY; GROWTH; METABOLISM; MICROENVIRONMENT; MICROFLUIDICS; PLATFORMS; INVASION; IMPACT;
D O I
10.1016/j.jtbi.2024.111893
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
The mechanisms underlying the formation of necrotic regions within avascular tumors are complex and poorly understood. In this paper, we investigate the formation of a necrotic core in a 3D tumor cell culture within a microfluidic device, considering oxygen, nutrients, and the microenvironment acidification by means of a computational-mathematical model. Our objective is to simulate cell processes, including proliferation and death inside a microfluidic device, according to the microenvironmental conditions. We employed approximation utilizing finite element models taking into account glucose, oxygen, and hydrogen ions diffusion, consumption and production, as well as cell proliferation, migration and death, addressing how tumor cells evolve under different conditions. The resulting mathematical model was examined under different scenarios, being capable of reproducing cell death and proliferation under different cell concentrations, and the formation of a necrotic core, in good agreement with experimental data reported in the literature. This approach not only advances our fundamental understanding of necrotic core formation but also provides a robust computational platform to study personalized therapeutic strategies, offering an important tool in cancer research and treatment design.
引用
收藏
页数:12
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