Human liver myofibroblasts during development and diseases with a focus on portal (myo)fibroblasts

Significance Statement

During liver injury, myofibroblasts appear principally deriving from the activation of local stromal cells such as portal fibroblasts and from hepatic stellate cells. Clearly, depending on the cause of the lesion (e.g. virus, alcohol) and of the primary location of the injury, the fibrogenic cells involved are different. The deactivation mechanisms of these different cells are not similar, and the question of the reversibility of the liver fibrosis/cirrhosis remains a burning issue. Indeed, after myofibroblastic differentiation, the portal fibroblasts do not seem to be able to reacquire a quiescent phenotype; in contrast, the hepatic stellate cells can modulate their myofibroblastic differentiation, and present pericyte-like features suggesting that they function as liver-specific pericytes participating in the regulation of sinusoidal blood pressure. Definitively, portal fibroblasts are involved in many pathological situations and must be considered as a major fibrogenic cell population beside the hepatic stellate cells. In addition, the portal (myo)fibroblasts play a pivotal role in the fetal liver development, as well as in wound healing, including tumoral stroma which could be assimilated to an overhealing wound.


Journal Reference

Front Physiol. 2015;6:173.

Lepreux S1, Desmoulière A2. 

[expand title=”Show Affiliations”]
  1. Department of Pathology, University Hospital of Bordeaux Bordeaux, France.
  2. Department of Physiology, Faculty of Pharmacy, University of Limoges Limoges, France.


Myofibroblasts are stromal cells mainly involved in tissue repair. These cells present contractile properties and play a major role in extracellular matrix deposition and remodeling. In liver, myofibroblasts are found in two critical situations. First, during fetal liver development, especially in portal tracts, myofibroblasts surround vessels and bile ducts during their maturation. After complete development of the liver, myofibroblasts disappear and are replaced in portal tracts by portal fibroblasts. Second, during liver injury, myofibroblasts re-appear principally deriving from the activation of local stromal cells such as portal fibroblasts and hepatic stellate cells or can sometimes emerge by an epithelial-mesenchymal transition process. After acute injury, myofibroblasts play also a major role during liver regeneration. While myofibroblastic precursor cells are well known, the spectrum of activation and the fate of myofibroblasts during disease evolution are not fully understood. Some data are in accordance with a possible deactivation, at least partial, or a disappearance by apoptosis. Despite these shadows, liver is definitively a pertinent model showing that myofibroblasts are pivotal cells for extracellular matrix control during morphogenesis, repair and fibrous scarring.

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Figure Legend In the liver, the portal fibroblasts located in the portal tract connective tissue around bile ducts, portal arteries, and portal veins, the second-layer cells, fibroblasts located around the smooth muscle cells and the endothelium of the centrolobular veins, and the hepatic stellate cells containing lipids droplets and located in the Disse’s space between the hepatocytes, can acquire a myofibroblastic phenotype. Myofibroblasts which present microfilament bundles and secrete large amounts of extracellular matrix, are involved in fibrosis and cirrhosis development.

Human liver myofibroblasts during development and diseases with a focus on portal (myo)fibroblasts. Global Medical Discovery