Department of Computer Science and Laboratory of Computational Physiology and High-Performance Computing (FISIOCOMP), Universidade Federal de Juiz de Fora, Juiz de Fora, Brazil.
Multiscale in Mechanical and Biological Engineering (M2BE), Mechanical Engineering Dept, University of Zaragoza, Zaragoza, Spain.
J Theor Biol. 2022 Aug 21;547:111173. doi: 10.1016/j.jtbi.2022.111173. Epub 2022 May 27.
Solid tumour growth depends on a host of factors which affect the cell life cycle and extracellular matrix vascularization that leads to a favourable environment. The whole solid tumour can either grow or wither in response to the action of the immune system and therapeutics. A personalised mathematical model of such behaviour must consider both the intra- and inter-cellular dynamics and the mechanics of the solid tumour and its microenvironment. However, such wide range of spatial and temporal scales can hardly be modelled in a single model, and require the so-called multiscale models, defined as orchestrations of single-scale component models, connected by relation models that transform the data for one scale to another. While multiscale models are becoming common, there is a well-established engineering approach to the definition of the scale separation, e.g., how the spatiotemporal continuum is split in the various component models. In most studies scale separation is defined as natural, linked to anatomical concepts such as organ, tissue, or cell; but these do not provide reliable definition of scales: for examples skeletal organs can be as large as 500 mm (femur), or as small as 3 mm (stapes). Here we apply a recently proposed scale-separation approach based on the actual experimental and computational limitations to a patient-specific model of the growth of neuroblastoma. The resulting multiscale model can be properly informed with the available experimental data and solved in a reasonable timeframe with the available computational resources.
实体瘤的生长取决于许多因素，这些因素会影响细胞生命周期和细胞外基质的血管生成，从而形成有利的环境。整个实体瘤可以根据免疫系统和治疗药物的作用而生长或枯萎。这种行为的个性化数学模型必须考虑细胞内和细胞间的动力学以及实体瘤及其微环境的力学特性。然而，如此广泛的时空尺度在单个模型中很难建模，并且需要所谓的多尺度模型，这些模型定义为由通过关系模型连接的单个尺度组件模型组成的协调，该关系模型将一个尺度的数据转换为另一个尺度。虽然多尺度模型越来越普遍，但定义尺度分离的方法已经得到了很好的确立，例如，时空连续体在各个组件模型中是如何划分的。在大多数研究中，尺度分离被定义为自然的，与器官、组织或细胞等解剖学概念相关联；但这些概念并不能提供可靠的尺度定义：例如，骨骼器官的大小可以像 500mm（股骨）一样大，也可以像 3mm（镫骨）一样小。在这里，我们将最近提出的基于实际实验和计算限制的尺度分离方法应用于神经母细胞瘤生长的患者特定模型。由此产生的多尺度模型可以使用可用的实验数据进行适当的告知，并使用可用的计算资源在合理的时间内求解。
