利用 Petri 网模拟肿瘤血管生成过程中的 iPSC 衍生内皮细胞转换

Adéla Šterberová, Andreea Dincu, Stijn Oudshoorn, Vincent van Duinen, Lu Cao
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摘要

整个过程十分复杂,涉及化学物质的产生和消耗、内皮细胞的转换以及细胞的相互作用、分裂和迁移。微流控细胞培养平台已被用于研究由人诱导多能干细胞(iPSC-ECs)衍生的内皮细胞在生理相关微环境中的血管生成。在本文中,我们将详细阐述如何定义一个管道,用于模拟 iPSC 内皮细胞在这种生物场景中的转化和过程。我们利用 Petrinets 的鲁棒性和简易性对细胞转化和相关约束进行建模。虽然该管道不能捕捉到肿瘤血管生成的全部复杂性,但我们能够利用这种概念上简化的解决方案捕捉到肿瘤血管生成过程中内皮细胞转化的本质。
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Modeling iPSC-derived Endothelial Cell Transition in Tumor Angiogenesis using Petri Nets
Tumor angiogenesis concerns the development of new blood vessels supplying the necessary nutrients for the further development of existing tumor cells. The entire process is complex, involving the production and consumption of chemicals, endothelial cell transitions as well as cell interactions, divisions, and migrations. Microfluidic cell culture platform has been used to study angiogenesis of endothelial cells derived from human induced pluripotent stem cells (iPSC-ECs) for a physiological relevant micro-environment. In this paper, we elaborate on how to define a pipeline for simulating the transformation and process that an iPSC-derived endothelial cell goes through in this biological scenario. We leverage the robustness and simplicity of Petri nets for modeling the cell transformation and associated constraints. The environmental and spacial factors are added using custom 2-dimensional grids. Although the pipeline does not capture the entire complexity of tumor angiogenesis, we are able to capture the essence of endothelial cell transitions in tumor angiogenesis using this conceptually simplified solution.
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