Fibroblasts and myofibroblasts.

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Fibroblasts and myofibroblasts.pdf

Abstract

Fibroblasts are found in most tissues of the body. They exhibit several phenotypes including non-contractile fibroblasts, contractile myofibroblasts, and intermediate phenotypes including the protomyofibroblast. Fibroblasts are metabolically active cells which play critical roles regulating extracellular matrices, interstitial fluid volume and pressure, and wound healing. Fibroblast numbers can be maintained or expanded by proliferation of resident populations but in addition, recent evidence indicates they can also be derived through epithelial-mesenchymal transition or from circulating and tissue-derived mesenchymal stem cells.

Many diseases are associated with dysregulation of the injury repair response and fibroblast function, leading to increased or decreased deposition of extracellular matrix proteins, altered tissue architecture, impaired function and in some cases significant morbidity and mortality. There are currently no specific therapies that target fibroblast-associated pathology but increasing knowledge of pathological mechanisms has led to development of new agents providing hope for improved treatment of these diseases.

Fig. 1. The source and function of fibroblasts in normal and pathological states. 

Origin and plasticity: Fibroblasts exist as several morphological phenotypes ranging from the extremes of the non-contractile fibroblast to the -smooth muscle actin stress fibre containing contractile myofibroblast together with an intermediate phenotype which has been termed the protomyofibroblast. Fibroblasts can transdifferentiate into myofibroblasts and there is some evidence to suggest the process may be reversible to at least some extent. Fibroblast populations can be maintained or expanded by proliferation of existing populations, or derived from epithelial-mesenchymal transition, circulating bone marrow-derived fibrocytes or from tissue-derived stem cells. There is also evidence that fibroblasts can undergo mesenchymal-epithelial transition and it has recently been shown that genetic programmes can be induced in fibroblasts to convert them into pluripotent stem cells. 

Function: Major functions of fibroblasts/myofibroblasts include: synthesis and degradation of the multitude of glycoproteins which make up the specialised extracellular matrices of tissues and organs of the body which contribute to their specific functions; regulation through cell–matrix interactions of interstitial fluid volume, pressure and appropriate levels of tissue contraction for optimum function; playing a critical role in wound healing through cell–cell and cell–matrix interactions, production and response to mediators, modulation of extracellular matrix metabolism, wound contraction and scar resolution. 

Pathology: Dysregulated or inappropriate fibroblast function is associated with pathologies in which diminished or excess extracellular matrix deposition, or inappropriate tissue contraction is a feature. Such conditions affect almost all tissues and organs of the body, examples of which are included in the figure.

[문형철]

Fibroblasts are found in most tissues of the body. They exhibit several phenotypes including non-contractile fibroblasts, contractile myofibroblasts, and intermediate phenotypes including the protomyofibroblast. Fibroblasts are metabolically active cells which play critical roles regulating extracellular matrices, interstitial fluid volume and pressure, and wound healing. Fibroblast numbers can be maintained or expanded by proliferation of resident populations but in addition, recent evidence indicates they can also be derived through epithelial-mesenchymal transition or from circulating and t