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Extracellular matrix bioengineering and systems biology approaches in liver disease

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Systems and Synthetic Biology

Abstract

The extracellular matrix (ECM) in the liver as well as in many organs comprises a peripheral network linking numerous macromolecules typically classified into collagens, microfibrillar proteins, proteoglycans, chemokines, growth factors and glycoproteins. In addition to its role as an essential structural and physiological component, it plays a vital role in driving key cellular events such as cell adhesion, migration, proliferation, differentiation and survival. Any structural inherited or acquired defect and/or metabolic or pathologic alteration in the hepatic ECM may cause cellular and organ responses leading to the development or progression of liver disease. Therefore, the ECM molecules are key players in tissue engraftment and in the pathophysiology of liver disease. In this review we provide a snapshot on current efforts for understanding its role in physiological and non-physiological states, by describing how tissue engineering platforms can enhance in vitro and in vivo models of liver disease, by providing examples where bioengineered ECM can serve as systems biology approaches to study the ECM, and then by evaluating pathological protein regulatory networks in the liver using systems biology tools. These approaches hold great promise for future research.

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Abbreviations

ECM:

Extracellular matrix

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Acknowledgments

US Public Health Service Grants 5R01DK069286-05 from the National Institute of Diabetes and Digestive and Kidney Diseases, 3R01AA017733-03, 3R01AA017733-02S1, 1P20AA017067-03 and 1P20AA017067-02S1 from the National Institute on Alcohol Abuse and Alcoholism (to NN). Swiss National Science Foundation grants CR32I3_125426/1 and CR23I2_125290, European Young Investigator (EURYI) award (PE002-117115/1), European grant FP7-NMP-2007-LARGE-1 and a grant from the Juvenile Diabetes Research Foundation JDRF 41-2009-775 (to MPL).

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Authors and Affiliations

  1. Department of Medicine, Division of Liver Diseases, Mount Sinai School of Medicine, Box 1123, 1425 Madison Avenue, Room 11-76, New York, NY, 10029, USA

    Natalia Nieto

  2. Laboratory of Stem Cell Bioengineering, Institute of Bioengineering, School of Life Sciences, Station 15. Bldg. Al 1109, Ecole Polytechnique Fédérale de Lausanne, 1015, Lausanne, Switzerland

    Matthias P. Lutolf

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  1. Natalia Nieto
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Correspondence to Natalia Nieto.

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Nieto, N., Lutolf, M.P. Extracellular matrix bioengineering and systems biology approaches in liver disease. Syst Synth Biol 5, 11–20 (2011). https://doi.org/10.1007/s11693-011-9085-4

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