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Hepatic stellate cells ( HSC), also known as perisinusoidal cells or Ito cells (earlier lipocytes or fat-storing cells), are found in the perisinusoidal space of the liver, also known as the space of Disse (a small area between the Liver sinusoid and ). The stellate cell is the major cell type involved in liver fibrosis, which is the formation of scar in response to liver damage; in addition these cells store and concentrate vitamin A.
Besides storing Vitamin A, quiescent hepatic stellate cells maintain liver homeostasis by controlling liver zonation and function through the secretion of R-spondin 3, a key regulator of the WNT pathway. Recent evidence suggests a role as a liver-resident antigen-presenting cell, presenting lipid antigens to and stimulating proliferation of NKT cells.
When the liver is damaged, stellate cells can change into an activated state. The activated stellate cell is characterized by proliferation, contractility, and chemotaxis. This change is seen as a transdifferentiation whereby the cells lose their stellate shape and acquire that of . This state of the stellate cell is the main source of extracellular matrix production in liver injury. This attribute makes it a key factor in the pathophysiology of the liver. The amount of stored vitamin A decreases progressively in liver injury. The activated stellate cell as a myofibroblast is also responsible for secreting components of the extracellular matrix including collagen that can promote the development of fibrosis and the formation of scar tissue. Continued fibrosis is thought to be responsible for the development of cirrhosis and liver cancer.
Studies have also shown that in vivo activation of hepatic stellate cells by agents causing liver fibrosis can eventually lead to senescence in these cells, marked by increased SA-beta-galactosidase staining, as well as p53 accumulation and activation of Rb—hallmarks of cellular senescence. Senescent hepatic stellate cells have been demonstrated to limit liver fibrosis by activating interactions with NK cells. Senescence of hepatic stellate cells could prevent progression of liver fibrosis, although this has not been implemented as a therapy, and would carry the risk of hepatic dysfunction.
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