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全仓鼠胰岛中水和溶质转运的数学模型构建与验证

Mathematical model formulation and validation of water and solute transport in whole hamster pancreatic islets.

作者信息

Benson James D, Benson Charles T, Critser John K

机构信息

Department of Mathematical Sciences, Northern Illinois University, DeKalb, IL 60178, USA.

Eli Lilly & Co., Lilly Corporate Center, Indianapolis, IN 46285, USA.

出版信息

Math Biosci. 2014 Aug;254:64-75. doi: 10.1016/j.mbs.2014.06.003. Epub 2014 Jun 17.

Abstract

Optimization of cryopreservation protocols for cells and tissues requires accurate models of heat and mass transport. Model selection often depends on the configuration of the tissue. Here, a mathematical and conceptual model of water and solute transport for whole hamster pancreatic islets has been developed and experimentally validated incorporating fundamental biophysical data from previous studies on individual hamster islet cells while retaining whole-islet structural information. It describes coupled transport of water and solutes through the islet by three methods: intracellularly, intercellularly, and in combination. In particular we use domain decomposition techniques to couple a transmembrane flux model with an interstitial mass transfer model. The only significant undetermined variable is the cellular surface area which is in contact with the intercellularly transported solutes, Ais. The model was validated and Ais determined using a 3×3 factorial experimental design blocked for experimental day. Whole islet physical experiments were compared with model predictions at three temperatures, three perfusing solutions, and three islet size groups. A mean of 4.4 islets were compared at each of the 27 experimental conditions and found to correlate with a coefficient of determination of 0.87±0.06 (mean ± SD). Only the treatment variable of perfusing solution was found to be significant (p<0.05). We have devised a model that retains much of the intrinsic geometric configuration of the system, and thus fewer laboratory experiments are needed to determine model parameters and thus to develop new optimized cryopreservation protocols. Additionally, extensions to ovarian follicles and other concentric tissue structures may be made.

摘要

细胞和组织冷冻保存方案的优化需要精确的热质传递模型。模型的选择通常取决于组织的结构。在此,我们开发了一个关于仓鼠整个胰岛水和溶质转运的数学和概念模型,并通过实验进行了验证,该模型整合了先前对单个仓鼠胰岛细胞研究的基础生物物理数据,同时保留了整个胰岛的结构信息。它通过三种方式描述水和溶质在胰岛中的耦合转运:细胞内、细胞间以及两者结合。特别地,我们使用区域分解技术将跨膜通量模型与间质传质模型耦合起来。唯一显著的未确定变量是与细胞间转运溶质接触的细胞表面积(A_{is})。使用针对实验日进行分组的(3×3)析因实验设计对模型进行验证并确定(A_{is})。在三个温度、三种灌注溶液和三个胰岛大小组的条件下,将整个胰岛的物理实验与模型预测进行比较。在(27)个实验条件中的每一个条件下,平均比较了(4.4)个胰岛,发现其相关系数的决定系数为(0.87±0.06)(均值±标准差)。仅发现灌注溶液的处理变量具有显著性((p<0.05))。我们设计了一个保留系统大部分固有几何结构的模型,因此确定模型参数以及开发新的优化冷冻保存方案所需的实验室实验更少。此外,该模型还可扩展应用于卵巢卵泡和其他同心组织结构。

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