Non-local models for the formation of hepatocyte-stellate cell aggregates
Non-local models for the formation of hepatocyte-stellate cell aggregates
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DOI：
10.1016/j.jtbi.2010.08.013
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发表时间：
2010-11-07
影响因子：
2
通讯作者：
Byrne, H. M.
中科院分区：
文献类型：
--
作者：
Green, J. E. F.;Waters, S. L.;Byrne, H. M.
肝细胞聚集体可以通过将肝细胞与星状细胞共培养而在体外生长。该方法导致比仅肝细胞培养物更快速的聚集，并且似乎增强了细胞活力和肝脏特异性功能标志物的表达。我们考虑了聚集体形成的早期阶段，并开发了一个新的数学模型来研究星状细胞在促进聚集体形成中的作用的两个替代假设（基于实验文献中的证据）。在假设1下，每个种群产生影响另一个种群的化学信号，并且增强的聚集是由于趋化性。假设2断言两种细胞类型之间的相互作用是通过直接的物理接触：星状体延伸长的细胞过程，将肝细胞拉成聚集体。在这两种假设下，肝细胞被它们自身产生的化学物质所吸引，并且细胞可以由于过度拥挤而受到排斥力。我们制定非本地（积分-偏微分）方程来描述细胞的密度，这是耦合到化学浓度的反应扩散方程。使用线性稳定性分析和数值模拟相结合的模型在每个假设下的行为进行了研究。我们的研究结果表明，如何聚集的初始速率取决于细胞接种率，以及如何分布的聚集体内的细胞取决于细胞类型之间的吸引力和排斥力的相对强度。根据我们的研究结果，我们建议可以进行实验来区分这两种假设。(C)2010爱思唯尔有限公司版权所有。
Liver cell aggregates may be grown in vitro by co-culturing hepatocytes with stellate cells. This method results in more rapid aggregation than hepatocyte-only culture, and appears to enhance cell viability and the expression of markers of liver-specific functions. We consider the early stages of aggregate formation, and develop a new mathematical model to investigate two alternative hypotheses (based on evidence in the experimental literature) for the role of stellate cells in promoting aggregate formation. Under Hypothesis 1, each population produces a chemical signal which affects the other, and enhanced aggregation is due to chemotaxis. Hypothesis 2 asserts that the interaction between the two cell types is by direct physical contact: the stellates extend long cellular processes which pull the hepatocytes into the aggregates. Under both hypotheses, hepatocytes are attracted to a chemical they themselves produce, and the cells can experience repulsive forces due to overcrowding. We formulate non-local (integro-partial differential) equations to describe the densities of cells, which are coupled to reaction-diffusion equations for the chemical concentrations. The behaviour of the model under each hypothesis is studied using a combination of linear stability analysis and numerical simulations. Our results show how the initial rate of aggregation depends upon the cell seeding ratio, and how the distribution of cells within aggregates depends on the relative strengths of attraction and repulsion between the cell types. Guided by our results, we suggest experiments which could be performed to distinguish between the two hypotheses. (C) 2010 Elsevier Ltd. All rights reserved.