Widera, Agata

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EXCLI Journal 2014;13:1289-1291 – ISSN 1611-2156 Received: December15, 2014, accepted: December 16, 2014, published: December 17, 2014   1289 Guest editorial: INTEGRATED SPATIOTEMPORAL-METABOLIC MODELLING BRIDGES THE GAP BETWEEN METABOLISM ON THE  CELLULAR LEVEL AND ORGAN FUNCTION  Agata Widera  Leibniz Institut für Arbeitsforschung an der TU Dortmund,  Leibniz Research Centre for Working Environment and Human Factors (IfADo),  Ardeystrasse 67, 44139 Dortmund, Germany; widera@ifado.de    Recently, Schliess et al. (2014) have in-troduced a novel concept of spatiotemporal modelling. This work is of general interest, because it offers a possibility to bridge the level of metabolic functions at the subcellu-lar level to tissue architecture and organ function. The authors used an already estab-lished spatiotemporal model of a liver lobule (Hoehme et al., 2010; 2007). This model simulates the position and coordinated movement of all hepatocytes in a representa-tive lobule during the destruction and regen-eration process after intoxication with hepa-totoxic compounds. Moreover, it contains the microvessel of the liver lobule that al-lows simulation of perfusion and dry transport. The authors used this model to ad-ditionally integrate metabolic process into the simulated hepatocytes (Schliess et al., 2014). Metabolic pathways of ammonia me-tabolism, the urea cycle in periportal and glutamine synthetase in the pericentral com-portment of the liver lobule, were modelled as differential equations and integrated into the hepatocytes of the spatiotemporal model. The resulting integrated model allows the simulation of ammonia and its metabolites in the liver vein (the ‘liver outflow’) for a given concentration in the portal vein (the ‘liver inflow’). Moreover, the model predicts to which degree a certain extent or pattern of liver tissue destruction will compromise ammonia detoxification. This novel tech-nique of integrated spatiotemporal tissue modelling may have a major impact on stud-ies of organ toxicity in future (Wierling, 2014; Godoy et al., 2013; Drasdo et al., 2014; Hammad et al., 2014). Currently, stud-ies on hepatotoxicity are often performed in vivo in rodents (Nussler et al., 2014; Zhang et al., 2013; Ghallab, 2013; Kanda et al., 2008; Monteiro et al., 2013; Köhle et al., 2008; Jaeschke et al., 2012; van Kesteren et al., 2013; Hammad et al., 2013; Hadi et al., 2013; Lo et al., 2012). On the other hand in vitro systems with hepatocytes represent a popular system to analyse molecular mecha-nisms (Messner et al., 2013; Godoy et al., 2009, 2010a, b; Hengstler et al., 2009; Klingmüller et al., 2006; Schyschka et al., 2013; Watzek et al., 2013; Muguruma et al., 2008; Grinberg et al., 2014; Schaap et al., 2012; Schug et al., 2013; Doktorova et al., 2012a, b; Ilkavets, 2013; Gagné et al., 2012; Fraczek et al., 2013; Fernandes et al., 2003). Although cultivated hepatocytes represent a valuable tool to qualitatively study molecular mechanisms it still is difficult to extrapolate their impact at the organ level. The work of Schliess et al. (2014) is a first step in estab-lishing modelling techniques that bridge the levels of intra or even subcellular metabolic pathways to the functionality and metabolic performance of entire organs.  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Integrated spatiotemporal-metabolic modelling bridges the gap between metabolism on the cellular level and organ function

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Integrated spatiotemporal-metabolic modelling bridges the gap between metabolism on the cellular level and organ function

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