FEM-based oxygen consumption and cell viability models for avascular pancreatic islets
FEM-based oxygen consumption and cell viability models for avascular pancreatic islets
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DOI：
10.1186/1742-4682-6-5
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发表时间：
2009-04-16
影响因子：
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通讯作者：
Buchwald, Peter
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作者：
Buchwald, Peter
背景：培养、移植或包封胰岛的功能和活力经常受到缺氧的限制，因为这些胰岛在分离过程中失去了血管，不得不依赖于梯度驱动的被动扩散，而这种扩散不能提供足够的氧气运输。胰岛（朗格汉斯胰岛）由于其相对较大的体积、较大的代谢需求和对缺氧的敏感性增加而特别容易受到影响。在这里，基于有限元方法（FEM）的多物理场模型进行了探索，以描述在静态和移动培养基中无血管胰岛的氧运输和细胞活力。方法：采用对流、扩散和不可压缩Navier-Stokes流体力学应用模式，在COMSOL Multiphysics中建立二维和三维模型。假设氧气消耗遵循michaelis - menten型动力学，并在局部浓度低于临界阈值时停止；在动态模型中，它也被允许随着葡萄糖浓度的增加而增加。结果：基于偏微分方程（PDE）的探索性细胞水平耗氧量和细胞活力模型结合了生理学上的现实假设，已经实现了以100、150和200 μ m直径的胰岛为代表的全尺寸细胞培养几何形状。计算出的氧浓度和胰岛内可能遭受缺氧相关坏死的区域，分别用于传统的烧瓶型培养、透氧硅橡胶膜底培养和具有流动介质和不同传入葡萄糖水平的灌注室，并以相应的彩色编码图形和动画进行了详细说明。结论：作为初步估计，计算模型的结果与现有的实验证据在定量上很好地一致，并且它们证实，在培养过程中，缺氧通常是无血管化胰岛的一个问题，并可导致相当大的细胞死亡（坏死），特别是在较大的胰岛的核心区域。这种模型对于提高培养、移植或封装胰岛的功能和活力具有重要意义。目前的实现允许方便地扩展到真正的多物理场应用程序，解决耦合物理现象，如由于流动或移动介质引起的对流扩散和消耗。
Background: The function and viability of cultured, transplanted, or encapsulated pancreatic islets is often limited by hypoxia because these islets have lost their vasculature during the isolation process and have to rely on gradient-driven passive diffusion, which cannot provide adequate oxygen transport. Pancreatic islets (islets of Langerhans) are particularly susceptible due to their relatively large size, large metabolic demand, and increased sensitivity to hypoxia. Here, finite element method (FEM) based multiphysics models are explored to describe oxygen transport and cell viability in avascular islets both in static and in moving culture media.Methods: Two-and three-dimensional models were built in COMSOL Multiphysics using the convection and diffusion as well as the incompressible Navier-Stokes fluid dynamics application modes. Oxygen consumption was assumed to follow Michaelis-Menten-type kinetics and to cease when local concentrations fell below a critical threshold; in a dynamic model, it was also allowed to increase with increasing glucose concentration.Results: Partial differential equation (PDE) based exploratory cellular-level oxygen consumption and cell viability models incorporating physiologically realistic assumptions have been implemented for fully scaled cell culture geometries with 100, 150, and 200 mu m diameter islets as representative. Calculated oxygen concentrations and intra-islet regions likely to suffer from hypoxia-related necrosis obtained for traditional flask-type cultures, oxygen-permeable silicone-rubber membrane bottom cultures, and perifusion chambers with flowing media and varying incoming glucose levels are presented in detail illustrated with corresponding colour-coded figures and animations.Conclusion: Results of the computational models are, as a first estimate, in good quantitative agreement with existing experimental evidence, and they confirm that during culture, hypoxia is often a problem for non-vascularised islet and can lead to considerable cell death (necrosis), especially in the core region of larger islets. Such models are of considerable interest to improve the function and viability of cultured, transplanted, or encapsulated islets. The present implementation allows convenient extension to true multiphysics applications that solve coupled physics phenomena such as diffusion and consumption with convection due to flowing or moving media.