CNR Institute of Clinical Physiology , Pisa , Italy ; Interdepartmental Research Center "E. Piaggio", University of Pisa , Pisa , Italy.
Interdepartmental Research Center "E. Piaggio", University of Pisa , Pisa , Italy.
Front Bioeng Biotechnol. 2014 Dec 17;2:74. doi: 10.3389/fbioe.2014.00074. eCollection 2014.
Intelligent in vitro models able to recapitulate the physiological interactions between tissues in the body have enormous potential as they enable detailed studies on specific two-way or higher order tissue communication. These models are the first step toward building an integrated picture of systemic metabolism and signaling in physiological or pathological conditions. However, the rational design of in vitro models of cell-cell or cell-tissue interaction is difficult as quite often cell culture experiments are driven by the device used, rather than by design considerations. Indeed, very little research has been carried out on in vitro models of metabolism connecting different cell or tissue types in a physiologically and metabolically relevant manner. Here, we analyze the physiological relationship between cells, cell metabolism, and exchange in the human body using allometric rules, downscaling them to an organ-on-a-plate device. In particular, in order to establish appropriate cell ratios in the system in a rational manner, two different allometric scaling models (cell number scaling model and metabolic and surface scaling model) are proposed and applied to a two compartment model of hepatic-vascular metabolic cross-talk. The theoretical scaling studies illustrate that the design and hence relevance of multi-organ models is principally determined by experimental constraints. Two experimentally feasible model configurations are then implemented in a multi-compartment organ-on-a-plate device. An analysis of the metabolic response of the two configurations demonstrates that their glucose and lipid balance is quite different, with only one of the two models recapitulating physiological-like homeostasis. In conclusion, not only do cross-talk and physical stimuli play an important role in in vitro models, but the numeric relationship between cells is also crucial to recreate in vitro interactions, which can be extrapolated to the in vivo reality.
能够重现体内组织之间生理相互作用的智能体外模型具有巨大的潜力，因为它们能够对特定的双向或更高阶组织通讯进行详细研究。这些模型是构建生理或病理条件下系统代谢和信号传递综合图的第一步。然而，设计细胞-细胞或细胞-组织相互作用的体外模型具有挑战性，因为细胞培养实验通常是由所用设备驱动的，而不是由设计考虑驱动的。事实上，很少有研究致力于以生理上和代谢上相关的方式连接不同细胞或组织类型的代谢体外模型。在这里，我们使用比例缩放规则分析细胞、细胞代谢和人体中物质交换之间的生理关系，并将其缩小到器官板上的装置。特别是，为了以合理的方式在系统中建立适当的细胞比例，提出并应用了两种不同的比例缩放模型（细胞数量缩放模型和代谢与表面缩放模型）到肝血管代谢串扰的两室模型中。理论比例缩放研究表明，多器官模型的设计和因此的相关性主要取决于实验限制。然后在多腔室器官板装置中实施了两种实验可行的模型配置。对两种配置的代谢响应分析表明，它们的葡萄糖和脂质平衡非常不同，只有两种模型中的一种再现了类似生理的动态平衡。总之，不仅串扰和物理刺激在体外模型中起着重要作用，而且细胞之间的数量关系对于重现体外相互作用也至关重要，这可以外推到体内现实。
