Hepatic Stellate Cells (Ito Cells)

Stellate cells reside in the liver within the space of Disse, that area between sinusoidal endothelial cells and the surface of hepatocytes, and thereby are intimately associated with both of those cell types. They constitute roughly 5% of the cells in the liver. In addition to their role in responding to hepatic injury, stellate cells in the healthy liver are the major storage site in the body for vitamin A.

Stellate cells provide the liver with an ability to respond to injury and heal certain types of damage. However, repeated insults result in long lasting fibrosis, which impairs many aspects of hepatic function.

In a normal, healthy liver, stellate cells are quiescent. When the liver is damaged by toxins or virus infection, hepatocytes and immune cells release factors that induce stellate cells to undergo a dramatic transformation into what is referred to as the activated state. Morphologically, the activated cells assume a myofibroblast-like morphology, but more importantly, they start to secrete a battery of extracellular matrix proteins that includes collagens, glycoproteins and proteoglycans. This activation process is also associated with loss of vitamin A storage. This is a useful response in protecting and facilitating healing within a damaged liver. The problem arises when the source of injury is chronic - in that case, stellate cells remain activated and secrete collagen to the point that the liver becomes fibrotic and hepatic function declines. Chronic hepatic fibrosis is a very serious disease that affects numerous systems and ultimately leads to liver failure due to cirrhosis.

Stellate cells are now recognized as having a myriad of functions other than simply responding to liver injury and inducing fibrosis. These versatile cells are known to play a critical role in development of the liver, in liver regeneration, and in modulating immunologic reactions within the liver. Considering all of these processes, it is not surprising that efforts to control stellate cell function is an active area of research.

References and Reviews

• Friedman SL. Hepatic stellate cells: Protean, multifunctional, and enigmatic cells of the liver. Physiol Rev. 2008; 88:125–172.
• Senoo H, Yoshikawa K, Morii M, et al. Hepatic stellate cell (vitamin A‐storing cell) and its relative – past, present and future. Cell Biol Internat. 2010; 34:1247-72.
• Yin C, Evason KJ, Asahina K, Stainier DYR. Hepatic stellate cells in liver development, regeneration, and cancer. J Clin Invest. 2013; 123:1902-1910.

Updated July 2019. Send comments to Richard.Bowen@colostate.edu