Hepatic stellate cell | |
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Details | |
Location | Perisinusoidal space of liver |
Identifiers | |
Latin | cellula perisinusoidalis; cellula accumulans adipem |
MeSH | D055166 |
TH | H3.04.05.0.00013 |
Anatomical terms of microanatomy |
Hepatic stellate cells (HSC), also known as perisinusoidal cells or Ito cells (earlier lipocytes or fat-storing cells), are pericytes found in the perisinusoidal space of the liver, also known as the space of Disse (a small area between the sinusoids and hepatocytes). The stellate cell is the major cell type involved in liver fibrosis, which is the formation of scar tissue in response to liver damage, in addition these cells store and concentrate vitamin A.
Hepatic stellate cells can be selectively stained with gold chloride, but their distinguishing feature in routine histological preparations is the presence of multiple lipid droplets in their cytoplasm. [1] Cytoglobin expression has been shown to be a specific marker with which hepatic stellate cells can be distinguished from portal myofibroblasts in the damaged human liver. [2] In murine (rats, mice) liver, reelin expressed by Ito cells has been shown to be a reliable marker in discerning them from other myofibroblasts. [3] The expression of reelin is increased after liver injury.
In normal liver, stellate cells are described as being in a quiescent state. Quiescent stellate cells represent 5-8% of the total number of liver cells. [4] Each cell has several long cytoplasmic protrusions that extend from the cell body and wrap around the sinusoids. [5] The lipid droplets in the cell body store vitamin A as retinyl palmitate. [6] Hepatic stellate cells store 50–80% of the body's vitamin A. [6]
The function and role of quiescent hepatic stellate cells is unclear. Recent evidence suggests a role as a liver-resident antigen-presenting cell, presenting lipid antigens to and stimulating proliferation of NKT cells. [7]
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 myofibroblasts. [8] [6] This state of the stellate cell is the main source of extracellular matrix production in liver injury. [9] This attribute makes it a key factor in the pathophysiology of the liver. The amount of stored vitamin A decreases progressively in liver injury. [1] 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. [10] [11]
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. [12] [13] 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. [14]
The cells of Ito were named for Toshio Ito, a twentieth-century Japanese physician, who introduced a fat-staining method to identify the "fat-storing cells" of the liver. [15] [16]
A hepatocyte is a cell of the main parenchymal tissue of the liver. Hepatocytes make up 80% of the liver's mass. These cells are involved in:
Portal hypertension is defined as increased portal venous pressure, with a hepatic venous pressure gradient greater than 5 mmHg. Normal portal pressure is 1–4 mmHg; clinically insignificant portal hypertension is present at portal pressures 5–9 mmHg; clinically significant portal hypertension is present at portal pressures greater than 10 mmHg. The portal vein and its branches supply most of the blood and nutrients from the intestine to the liver.
Fibrosis, also known as fibrotic scarring, is a pathological wound healing in which connective tissue replaces normal parenchymal tissue to the extent that it goes unchecked, leading to considerable tissue remodelling and the formation of permanent scar tissue.
Fatty liver disease (FLD), also known as hepatic steatosis and steatotic liver disease (SLD), is a condition where excess fat builds up in the liver. Often there are no or few symptoms. Occasionally there may be tiredness or pain in the upper right side of the abdomen. Complications may include cirrhosis, liver cancer, and esophageal varices.
Kupffer cells, also known as stellate macrophages and Kupffer–Browicz cells, are specialized cells localized in the liver within the lumen of the liver sinusoids and are adhesive to their endothelial cells which make up the blood vessel walls. Kupffer cells comprise the largest population of tissue-resident macrophages in the body. Gut bacteria, bacterial endotoxins, and microbial debris transported to the liver from the gastrointestinal tract via the portal vein will first come in contact with Kupffer cells, the first immune cells in the liver. It is because of this that any change to Kupffer cell functions can be connected to various liver diseases such as alcoholic liver disease, viral hepatitis, intrahepatic cholestasis, steatohepatitis, activation or rejection of the liver during liver transplantation and liver fibrosis. They form part of the mononuclear phagocyte system.
Plasminogen activator inhibitor-1 (PAI-1) also known as endothelial plasminogen activator inhibitor is a protein that in humans is encoded by the SERPINE1 gene. Elevated PAI-1 is a risk factor for thrombosis and atherosclerosis.
Hypervitaminosis A refers to the toxic effects of ingesting too much preformed vitamin A. Symptoms arise as a result of altered bone metabolism and altered metabolism of other fat-soluble vitamins. Hypervitaminosis A is believed to have occurred in early humans, and the problem has persisted throughout human history. Toxicity results from ingesting too much preformed vitamin A from foods, supplements, or prescription medications and can be prevented by ingesting no more than the recommended daily amount.
Transforming growth factor beta 1 or TGF-β1 is a polypeptide member of the transforming growth factor beta superfamily of cytokines. It is a secreted protein that performs many cellular functions, including the control of cell growth, cell proliferation, cell differentiation, and apoptosis. In humans, TGF-β1 is encoded by the TGFB1 gene.
CD1D is the human gene that encodes the protein CD1d, a member of the CD1 family of glycoproteins expressed on the surface of various human antigen-presenting cells. They are non-classical MHC proteins, related to the class I MHC proteins, and are involved in the presentation of lipid antigens to T cells. CD1d is the only member of the group 2 CD1 molecules.
A myofibroblast is a cell phenotype that was first described as being in a state between a fibroblast and a smooth muscle cell.
The perisinusoidal space is a space between a hepatocyte, and a sinusoid in the liver. It contains the blood plasma. Microvilli of hepatocytes extend into this space, allowing proteins and other plasma components from the sinusoids to be absorbed by the hepatocytes. Fenestration and discontinuity of the sinusoid endothelium facilitates this transport. The perisinusoidal space also contains hepatic stellate cells, which store vitamin A in characteristic lipid droplets.
A liver sinusoid is a type of capillary known as a sinusoidal capillary, discontinuous capillary or sinusoid, that is similar to a fenestrated capillary, having discontinuous endothelium that serves as a location for mixing of the oxygen-rich blood from the hepatic artery and the nutrient-rich blood from the portal vein.
Cytoglobin is the protein product of CYGB, a human and mammalian gene.
Cellular senescence is a phenomenon characterized by the cessation of cell division. In their experiments during the early 1960s, Leonard Hayflick and Paul Moorhead found that normal human fetal fibroblasts in culture reach a maximum of approximately 50 cell population doublings before becoming senescent. This process is known as "replicative senescence", or the Hayflick limit. Hayflick's discovery of mortal cells paved the path for the discovery and understanding of cellular aging molecular pathways. Cellular senescence can be initiated by a wide variety of stress inducing factors. These stress factors include both environmental and internal damaging events, abnormal cellular growth, oxidative stress, autophagy factors, among many other things.
Integrin alpha-11 is a protein that, in humans, is encoded by the ITGA11 gene.
The liver is a major metabolic organ exclusively found in vertebrate animals, which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and various other biochemicals necessary for digestion and growth. In humans, it is located in the right upper quadrant of the abdomen, below the diaphragm and mostly shielded by the lower right rib cage. Its other metabolic roles include carbohydrate metabolism, the production of hormones, conversion and storage of nutrients such as glucose and glycogen, and the decomposition of red blood cells.
Pancreatic stellate cells (PaSCs) are classified as myofibroblast-like cells that are located in exocrine regions of the pancreas. PaSCs are mediated by paracrine and autocrine stimuli and share similarities with the hepatic stellate cell. Pancreatic stellate cell activation and expression of matrix molecules constitute the complex process that induces pancreatic fibrosis. Synthesis, deposition, maturation and remodelling of the fibrous connective tissue can be protective, however when persistent it impedes regular pancreatic function.
Liver cytology is the branch of cytology that studies the liver cells and its functions. The liver is a vital organ, in charge of almost all the body’s metabolism. Main liver cells are hepatocytes, Kupffer cells, and hepatic stellate cells; each one with a specific function.
Perilipin 5, also known as Oxpatperilipin 5 or PLIN5, is a protein that belongs to perilipin family. This protein group has been shown to be responsible for lipid droplet's biogenesis, structure and degradation. In particular, Perilipin 5 is a lipid droplet-associated protein whose function is to keep the balance between lipolysis and lipogenesis, as well as maintaining lipid droplet homeostasis. For example, in oxidative tissues, muscular tissues and cardiac tissues, PLIN5 promotes association between lipid droplets and mitochondria.
Liver sinusoidal endothelial cells (LSECs) form the lining of the smallest blood vessels in the liver, also called the hepatic sinusoids. LSECs are highly specialized endothelial cells with characteristic morphology and function. They constitute an important part of the reticuloendothelial system (RES).