Animal and Human Models of Tissue Repair and Fibrosis: An Introduction.

Abstract

Reductionist cell culture systems are not only convenient but essential to understand molecular mechanisms of myofibroblast activation and action in carefully controlled conditions. However, tissue myofibroblasts do not act in isolation and the complexity of tissue repair and fibrosis in humans cannot be captured even by the most elaborate culture models. Over the past five decades, numerous animal models have been developed to study different aspects of myofibroblast biology and interactions with other cells and extracellular matrix. The underlying principles can be broadly classified into: (1) organ injury by trauma such as prototypical full thickness skin wounds or burns; (2) mechanical challenges, such as pressure overload of the heart by ligature of the aorta or the pulmonary vein; (3) toxic injury, such as administration of bleomycin to lungs and carbon tetrachloride to the liver; (4) organ infection with viruses, bacteria, and parasites, such as nematode infections of liver; (5) cytokine and inflammatory models, including local delivery or viral overexpression of active transforming growth factor beta; (6) lifestyle and metabolic models such as high-fat diet; and (7) various genetic models. We will briefly summarize the most widely used mouse models used to study myofibroblasts in tissue repair and fibrosis as well as genetic tools for manipulating myofibroblast repair functions in vivo.