Unraveling liver complexity from molecular to organ level: Challenges and perspectives

D'alessandro, L; Hoehme, Stefan; Henney, Adriano; Drasdo, Dirk; Klingmüller, Ursula

doi:10.1016/j.pbiomolbio.2014.11.005

Cited by 18 publications

(14 citation statements)

References 99 publications

(104 reference statements)

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“…Once blood leaves the lobules, it exits through the third vasculature structure, the hepatic vein [ 15 ]. At the lobule scale, several imaging techniques (scanning electron microscopy, confocal laser scanning, etc D’Alessandro et al, [ 16 ]; Hoehme et al [ 17 ]) can be used to quantify sinusoid structures.…”

Section: Methods and Modelsmentioning

confidence: 99%

Building a 3D Virtual Liver: Methods for Simulating Blood Flow and Hepatic Clearance on 3D Structures

et al. 2016

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In this paper, we develop a spatio-temporal modeling approach to describe blood and drug flow, as well as drug uptake and elimination, on an approximation of the liver. Extending on previously developed computational approaches, we generate an approximation of a liver, which consists of a portal and hepatic vein vasculature structure, embedded in the surrounding liver tissue. The vasculature is generated via constrained constructive optimization, and then converted to a spatial grid of a selected grid size. Estimates for surrounding upscaled lobule tissue properties are then presented appropriate to the same grid size. Simulation of fluid flow and drug metabolism (hepatic clearance) are completed using discretized forms of the relevant convective-diffusive-reactive partial differential equations for these processes. This results in a single stage, uniformly consistent method to simulate equations for blood and drug flow, as well as drug metabolism, on a 3D structure representative of a liver.

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Section: Methods and Modelsmentioning

confidence: 99%

Building a 3D Virtual Liver: Methods for Simulating Blood Flow and Hepatic Clearance on 3D Structures

et al. 2016

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“…The determination of those equations is a non-trivial task and in general they should be determined from experiments or might be inferred from agent-based models using averaging techniques [49,83,149,[226][227][228][229]. This branch is usually refered to as multiscale models within the mathematical and engineering community, and has to be distinguished from multi-level model which integrate components, mechanisms and information from different scales in one model [230]. It is likely however, that if one wants to capture the whole complexity of tissue dynamics, hybrid models will come into play.…”

Section: Hybrid Discrete-continuum Modelsmentioning

confidence: 99%

Simulating tissue mechanics with agent-based models: concepts, perspectives and some novel results

et al. 2015

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In this paper we present an overview of agentbased models that are used to simulate mechanical and physiological phenomena in cells and tissues, and we discuss underlying concepts, limitations, and future perspectives of these models. As the interest in cell and tissue mechanics increase, agent-based models are becoming more common the modeling community. We overview the physical aspects, complexity, shortcomings, and capabilities of the major agent-based model categories: lattice-based models (cellular automata, lattice gas cellular automata, cellular Potts models), off-lattice models (center-based models, deformable cell models, vertex models), and hybrid discrete-continuum models. In this way, we hope to assist future researchers in choosing a model for the phenomenon they want to model and understand. The article also contains some novel results.

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“…virtual-liver.de) (VLN) to more detailed vascular models of the hepatic sinusoids [46,47] and to multiscale and biophysically based models of physiological liver function [48,49]. Similar work is being done for the heart [40].…”

Section: Short-range Flowmentioning

confidence: 99%

A physiome interoperability roadmap for personalized drug development

et al. 2016

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One contribution of 12 to a theme issue 'The Human Physiome: a necessary key to the creative destruction of medicine'. The goal of developing therapies and dosage regimes for characterized subgroups of the general population can be facilitated by the use of simulation models able to incorporate information about inter-individual variability in drug disposition (pharmacokinetics), toxicity and response effect (pharmacodynamics). Such observed variability can have multiple causes at various scales, ranging from gross anatomical differences to differences in genome sequence. Relevant data for many of these aspects, particularly related to molecular assays (known as '-omics'), are available in online resources, but identification and assignment to appropriate model variables and parameters is a significant bottleneck in the model development process. Through its efforts to standardize annotation with consequent increase in data usability, the human physiome project has a vital role in improving productivity in model development and, thus, the development of personalized therapy regimes. Here, we review the current status of personalized medicine in clinical practice, outline some of the challenges that must be overcome in order to expand its applicability, and discuss the relevance of personalized medicine to the more widespread challenges being faced in drug discovery and development. We then review some of (i) the key data resources available for use in model development and (ii) the potential areas where advances made within the physiome modelling community could contribute to physiologically based pharmacokinetic and physiologically based pharmacokinetic/pharmacodynamic modelling in support of personalized drug development. We conclude by proposing a roadmap to further guide the physiome community in its on-going efforts to improve data usability, and integration with modelling efforts in the support of personalized medicine development.

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Unraveling liver complexity from molecular to organ level: Challenges and perspectives

Cited by 18 publications

References 99 publications

Building a 3D Virtual Liver: Methods for Simulating Blood Flow and Hepatic Clearance on 3D Structures

Building a 3D Virtual Liver: Methods for Simulating Blood Flow and Hepatic Clearance on 3D Structures

Simulating tissue mechanics with agent-based models: concepts, perspectives and some novel results

A physiome interoperability roadmap for personalized drug development

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