Improving the physiological realism of experimental models

Author:

Vinnakota Kalyan C.1,Cha Chae Y.2,Rorsman Patrik2,Balaban Robert S.3,La Gerche Andre4,Wade-Martins Richard56,Beard Daniel A.1,Jeneson Jeroen A. L.78ORCID

Affiliation:

1. Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, USA

2. Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Churchill Hospital, Oxford OX3 7LJ, UK

3. Laboratory of Cardiac Energetics, National Heart Lung Blood Institute, Bethesda, MD, USA

4. Baker IDI Heart and Diabetes Institute, Melbourne, Australia

5. Oxford Parkinson's Disease Centre, University of Oxford, Oxford, UK

6. Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK

7. Neuroimaging Centre, Division of Neuroscience, University Medical Center Groningen, Groningen, The Netherlands

8. Department of Radiology, Academic Medical Center Amsterdam, University of Amsterdam, Amsterdam, The Netherlands

Abstract

The Virtual Physiological Human (VPH) project aims to develop integrative, explanatory and predictive computational models (C-Models) as numerical investigational tools to study disease, identify and design effective therapies and provide an in silico platform for drug screening. Ultimately, these models rely on the analysis and integration of experimental data. As such, the success of VPH depends on the availability of physiologically realistic experimental models (E-Models) of human organ function that can be parametrized to test the numerical models. Here, the current state of suitable E-models, ranging from in vitro non-human cell organelles to in vivo human organ systems, is discussed. Specifically, challenges and recent progress in improving the physiological realism of E-models that may benefit the VPH project are highlighted and discussed using examples from the field of research on cardiovascular disease, musculoskeletal disorders, diabetes and Parkinson's disease.

Funder

National Heart and Lung Institute

National Institutes of Health

Welcome Trust

Publisher

The Royal Society

Subject

Biomedical Engineering,Biomaterials,Biochemistry,Bioengineering,Biophysics,Biotechnology

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