Hepatic stellate cells (HSC), also known as perisinusoidal cells or Ito cells (earlier ''lipocytes'' or ''fat-storing cells''), are

pericyte Pericytes (previously known as Rouget cells) are multi-functional mural cells of the microcirculation that wrap around the endothelial cells that line the capillaries throughout the body. Pericytes are embedded in the basement membrane of blood ca ...

s found in the

perisinusoidal space The perisinusoidal space (or space of Disse) is a location in the liver between a hepatocyte and a sinusoid. It contains the blood plasma. Microvilli of hepatocytes extend into this space, allowing proteins and other plasma components from the ...

of the

liver The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for ...

, also known as the space of Disse (a small area between the

sinusoid A sine wave, sinusoidal wave, or just sinusoid is a mathematical curve defined in terms of the ''sine'' trigonometric function, of which it is the graph. It is a type of continuous wave and also a smooth periodic function. It occurs often in ma ...

s and

hepatocyte 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: * Protein synthesis * Protein storage * Transformation of carbohydrates * Synthesis of cholesterol, ...

s). The stellate cell is the major cell type involved in liver

fibrosis 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 perma ...

, which is the formation of

scar tissue Scar tissue may refer to: Medicine * Scar, an area of fibrous tissue that replaces normal skin after injury * Granulation tissue, a product of healing in major wounds Film and television * ''Scar Tissue'' (1975 film), or ''Wanted: Babysitter'' ...

in response to liver damage.

Structure

Hepatic stellate cells can be selectively stained with

gold chloride Gold chloride can refer to: * Gold(I) chloride (gold monochloride), AuCl * Gold(I,III) chloride (gold dichloride, tetragold octachloride), Au4Cl8 * Gold(III) chloride (gold trichloride, digold hexachloride), Au2Cl6 * Chloroauric acid Chloroauric ...

, but their distinguishing feature in routine histological preparations is the presence of multiple lipid droplets in their

cytoplasm In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. The ...

Cytoglobin Cytoglobin is the protein product of CYGB, a human and mammalian gene. Cytoglobin is a globin molecule ubiquitously expressed in all tissues and most notably utilized in marine mammals. It was discovered in 2001 and named cytoglobin in 2002. It i ...

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. In murine (rats, mice) liver,

reelin Reelin, encoded by the ''RELN'' gene, is a large secreted extracellular matrix glycoprotein that helps regulate processes of neuronal migration and positioning in the developing brain by controlling cell–cell interactions. Besides this import ...

expressed by Ito cells has been shown to be a reliable marker in discerning them from other

myofibroblast A myofibroblast is a cell phenotype that was first described as being in a state between a fibroblast and a smooth muscle cell. Structure Myofibroblasts are contractile web-like fusiform cells that are identifiable by their expression of α-sm ...

s. The expression of reelin is increased after liver injury.

Function

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. Each cell has several long protrusions that extend from the cell body and wrap around the sinusoids. The

lipid Lipids are a broad group of naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids include ...

droplets in the cell body store

vitamin A Vitamin A is a fat-soluble vitamin and an essential nutrient for humans. It is a group of organic compounds that includes retinol, retinal (also known as retinaldehyde), retinoic acid, and several provitamin A carotenoids (most notably bet ...

retinol Retinol, also called vitamin A1, is a fat-soluble vitamin in the vitamin A family found in food and used as a dietary supplement. As a supplement it is used to treat and prevent vitamin A deficiency, especially that which results in xerophtha ...

ester In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides ar ...

. The function and role of quiescent hepatic stellate cells is unclear. Recent evidence suggests a role as a liver-resident

antigen-presenting cell An antigen-presenting cell (APC) or accessory cell is a cell that displays antigen bound by major histocompatibility complex (MHC) proteins on its surface; this process is known as antigen presentation. T cells may recognize these complexes using ...

, 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 Chemotaxis (from '' chemo-'' + ''taxis'') is the movement of an organism or entity in response to a chemical stimulus. Somatic cells, bacteria, and other single-cell or multicellular organisms direct their movements according to certain chemica ...

. 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 is also responsible for secreting

collagen Collagen () is the main structural protein in the extracellular matrix found in the body's various connective tissues. As the main component of connective tissue, it is the most abundant protein in mammals, making up from 25% to 35% of the whole ...

scar tissue, which can lead to

cirrhosis Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, and end-stage liver disease, is the impaired liver function caused by the formation of scar tissue known as fibrosis due to damage caused by liver disease. Damage causes tissue repai ...

. More recent studies have also shown that in vivo activation of hepatic stellate cells by agents causing liver fibrosis can eventually lead to

senescence Senescence () or biological aging is the gradual deterioration of functional characteristics in living organisms. The word ''senescence'' can refer to either cellular senescence or to senescence of the whole organism. Organismal senescence inv ...

in these cells, marked by increased SA-beta-galactosidase staining, as well as

p53 p53, also known as Tumor protein P53, cellular tumor antigen p53 (UniProt name), or transformation-related protein 53 (TRP53) is a regulatory protein that is often mutated in human cancers. The p53 proteins (originally thought to be, and often s ...

accumulation and activation of Rb–hallmarks of

cellular senescence 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 approxi ...

. Senescent hepatic stellate cells have been demonstrated to limit liver fibrosis by activating interactions with

NK cells Natural killer cells, also known as NK cells or large granular lymphocytes (LGL), are a type of cytotoxic lymphocyte critical to the innate immune system that belong to the rapidly expanding family of known innate lymphoid cells (ILC) and represen ...

. 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.

History

The cells of Ito were named for

Toshio Ito Toshio is a common masculine Japanese given name. Possible writings Toshio can be written using different kanji characters and can mean: *敏夫, "agile, man" *敏男, "agile, man" *敏雄, "agile, male" *俊夫, "sagacious, man" *俊雄, "sagaci ...

, a twentieth-century Japanese physician, who introduced a fat-staining method to identify the "fat-storing cells" of the liver.

References

External links

* * Liver Research at AU-KB
Stellate cell biology
{{Authority control Liver anatomy Human cells

Structure

Function

History

See also

References

External links