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Hybrid computational modeling of cell population and mass transfer dynamics in tissue growth processes.

机译：组织生长过程中细胞种群和传质动力学的混合计算模型。

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This work presents a comprehensive hybrid computer model simulating the cell population and mass transfer dynamics during tissue growth processes. The model has three major components: (a) a discrete algorithm simulating individual cell activities and cell-cell interactions; (b) transient, three-dimensional partial differential equations (PDE's) describing the convection, diffusion, consumption and, possibly, secretion of nutrients or other important substances in tissue systems; and (c) equations describing how cell behavior is modulated by the local concentration fields.; The hybrid model is first used to study the growth of bioartificial tissues under conditions leading to nutrient depletion. Simulation results indicate that large tissue size, low nutrient diffusivity, high cell uptake rate and low nutrient concentration in the culture media lead to severe transport limitations and have serious adverse effects on the growth rates and the structure of bioartificial tissues. The incorporation of perfusion channels is one of the proposed methods for alleviating diffusional limitations. However, the selection of optimal channel placement and size leads to an interesting optimization problem. Our results indicate the existence of an optimal channel diameter for each set of cell parameters and culture conditions. As diffusional limitations become more severe, larger perfusion channels are needed and the value of the achievable cell density decreases.; Finally, the hybrid model is used to study the acid-mediated growth of solid tumors. With its ability to describe the complex, three-dimensional vasculature of tissues invaded by tumors, our model represents a significant extension of previous two-dimensional studies. In addition to a three-dimensional capillary network generated from literature data, tree-like capillary networks with adjustable overall vascularity are generated using a bifurcating distributive algorithm in order to study the effect of host vascularity on tissue growth. Our simulations produce tumor growth curves similar to those observed clinically. The predicted range of tumor cell acid production rate shows better agreement with experimental values than existing two-dimensional models. Our model can also predict the universal existence of necrotic regions in large tumors.
机译：这项工作提出了一个全面的混合计算机模型，可以模拟组织生长过程中的细胞数量和传质动力学。该模型具有三个主要组成部分：（a）模拟单个细胞活动和细胞间相互作用的离散算法； （b）瞬态三维偏微分方程（PDE），描述组织系统中营养物或其他重要物质的对流，扩散，消耗以及可能的分泌； （c）描述局部浓度场如何调节细胞行为的方程。混合模型首先用于研究导致营养耗尽的条件下生物人工组织的生长。模拟结果表明，培养基中组织尺寸大，营养物质扩散率低，细胞摄取率高和营养物浓度低会导致严重的运输限制，并对生物人工组织的生长速度和结构产生严重的不利影响。灌注通道的合并是减轻扩散限制的建议方法之一。但是，选择最佳的通道位置和大小会导致一个有趣的优化问题。我们的结果表明，每组细胞参数和培养条件均存在最佳通道直径。随着扩散限制变得更加严重，需要更大的灌注通道并且可达到的细胞密度值降低。最后，使用杂交模型研究酸介导的实体瘤的生长。凭借其描述被肿瘤侵袭的组织的复杂三维血管系统的能力，我们的模型代表了先前二维研究的重要扩展。除了从文献数据中生成的三维毛细血管网络之外，还使用分叉分布算法生成具有可调整的总血管的树状毛细血管网络，以研究宿主血管性血管对组织生长的影响。我们的模拟产生的肿瘤生长曲线与临床观察的相似。与现有的二维模型相比，预测的肿瘤细胞酸产生率范围与实验值具有更好的一致性。我们的模型还可以预测大肿瘤中坏死区域的普遍存在。

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