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Stiffness and Hepatocytes Function In Vitro

  • Srivatsan KidambiEmail author
Chapter
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Abstract

Liver fibrosis is a wound-healing response to chronic liver injury such as alcoholic/nonalcoholic fatty liver disease, and viral hepatitis with no FDA-approved treatments. Liver fibrosis results in a continual accumulation of extracellular matrix (ECM) proteins and paves the way for replacement of parenchyma with non-functional scar tissue. During liver fibrosis, alterations in hepatocytes phenotype including apoptosis, oxidative stress, and loss of metabolic function have been shown to precede fibrosis and promote hepatic stellate cell activation. Specifically, hepatocyte death, as part of the original injury, triggers a cascade of events, including pathological accumulation of ECM leading to the increased tissue stiffness during liver injury. This chapter provides an overview of the interplay of hepatocytes with stiffness using in vitro models mimicking physiological and pathological matrix rigidity to provide insight into the pivotal changes in hepatocytes physiology and the extent to which it mediates the progression of liver fibrosis. Establishing the molecular aspects of hepatocytes in the light of fibrotic liver stiffness is valuable towards development of novel therapeutic and diagnostic targets of liver fibrosis.

Keywords

Liver stiffness Hepatocytes Fibrosis Metabolism Matrix Bio-mimetic models Mechanotransduction Mechanosensors Matrix Collagen Polydimethylsiloxane 

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© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Department of Chemical and Biomolecular EngineeringUniversity of NebraskaLincolnUSA
  2. 2.Fred and Pamela Buffett Cancer Center, University of Nebraska Medical CenterOmahaUSA
  3. 3.Nebraska Center for Integrated Biomolecular Communication, University of NebraskaLincolnUSA
  4. 4.Nebraska Center for the Prevention of Obesity Diseases, University of NebraskaLincolnUSA
  5. 5.Nebraska Center for Materials and Nanoscience, University of NebraskaLincolnUSA
  6. 6.Mary and Dick Holland Regenerative Medicine ProgramUniversity of Nebraska Medical CenterOmahaUSA

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