Stellate cells, Ito cells, stellate fat deposit cells, or hepatic lipocytes, are a type of cell found in the perisinusoidal space of Disse, an anatomical region of the liver.
The liver is the largest gland in the human body and is made up of specialized parenchymal cells, the hepatocytes, which are responsible for converting harmful and toxic substances into inert substances that are excreted by the bile.
Structure of the hepatic lobules (Source: Boumphreyfr via Wikimedia Commons)
Hepatocytes are arranged in liver tissue as hexagonal "lobules", which consist of rows of no more than one pair of cells that are grouped or stacked together, forming structures known as "anastomosing plaques."
In the space between each plate of hepatocytes, the hepatic sinusoids are achieved, which are nothing more than small capillaries through which the blood flows. Around these capillaries there is a lining of endothelial cells that prevents blood from the capillaries from coming into contact with the hepatocytes.
Between the layer of endothelial cells covering the sinusoids and the hepatocytes there is a space known as the perisinusoidal space of Disse; and it is there that the stellate cells are found, along with other cells and fibrous elements.
They were described in 1876 by the German scientist von Kupffer, but their functions were not clarified until 1951, 75 years later, by Ito. More than two decades later they were intimately associated with liver fibrosis pathology, and since then they have been studied extensively.
characteristics
Stellate cells or cells of Ito are cells that store fat in a particular region of the liver known as the perisinusoidal space or space of Disse, and therefore are also known as hepatic lipocytes.
They represent approximately 10% of the resident cells of the liver, occupying about 1.5% of its volume. One of its most special characteristics is the presence of multiple "drops" of vitamin A inside, particularly visible with some staining techniques.
Schematic representation of a stellate cell or Ito cell in the liver (Source: Gressner et al. Comparative Hepatology 2007 6: 7 doi: 10.1186 / 1476-5926-6-7 via Wikimedia Commons)
Its name has to do with the long dendrite-like cytoplasmic processes that allow direct contact with other stellate cells, as well as with the endothelial cells and the hepatocytes that surround them.
Through these cytoplasmic projections, stellate cells can exchange soluble molecules such as hormones and even neurotransmitters, as these are also found at the end of many nerve endings.
Its cell body has an elongated shape, inside which are oval or elongated nuclei. In addition to being packed with tiny droplets of vitamin A, a small Golgi complex near the nucleus and a well-developed endoplasmic reticulum are found in the cytoplasm.
They produce a wide variety of cytoskeletal and connective tissue proteins such as desmin, vimentin, actin, tubulin, fibronectin, collagen, and laminin.
Recent studies have shown that these cells have some phagocytic properties and functions and that they play an important role in the development of liver fibrosis.
Training
Stellate cells are highly heterogeneous, and since they present markers that are characteristic of a wide range of different origins, their ontogenetic origin has been an enigma since their discovery more than 150 years ago.
In human development, Ito cells are identified in the second half of the second month; and it has been suggested that they arise either from endodermal tissue or from mesenchymal heart tissue, a process strictly regulated by multiple factors.
The most accepted theory is that of cardiac tissue, where it is established that these cells come from a mesothelial progenitor, probably derived from the transverse mesenchymal septum, a transverse layer of cells that separates the pericardial and peritoneal cavities of the embryo.
However, the presence of stellate cells in various extrahepatic organs, as well as the existence of some stellate cells with neural characteristics, is difficult to explain by either of the two theories.
Parts
Like the rest of the cells of multicellular organisms, hepatic lipocytes or stellate cells have a perikaryon, soma or cell body, which is accompanied by the cytoplasmic processes or projections mentioned above.
The cytoplasmic projections of Ito cells have three surfaces: internal, external, and lateral. The internal one adheres to the basal surface of the epithelial sinusoidal cells, while the external one faces the space of Disse and has many micro-projections that are in contact with the hepatocytes.
The microprojections on the external face of the stellate cells have functions in the perception of chemotactic signals and their transmission for the generation of the contractile force that regulates sinusoidal blood flow.
The perikaryon or soma is found in the perisinusoidal space, in the remaining spaces between the parenchymal cells located in said region, and its diameter varies according to the species, the anatomical region and the physiological condition in which it is found.
Features
Ito cells are intimately associated with the progenitor or “stem” cell niche that gave rise to them. They are thought to support the proliferation and development of the latter.
The secretion of morphogenic substances makes the stellate cells play an important role in the development (organogenesis) and regeneration of the liver.
They also work in the storage of retinoids (derivatives of vitamin A), which are important factors for the growth of epithelial cells.
In addition, they participate in the maintenance of the homeostasis of the extracellular matrix, essential for liver functions, as well as in the segregation of different molecules equally important for this process, such as:
- Growth factors
- Neurotrophic factors and their receptors
- Vasoconstrictors
- Peptides, among others.
They have functions in detoxification and the hepatic metabolism of drugs, since they express the enzymes alcohol and acetaldehyde dehydrogenases.
The activation of these cells in a "dormant" or "quiescent" state promotes various changes in the patterns of genetic and phenotypic expression in the cells that participate in the repair of the damaged liver.
They also participate in the regulation of sinusoidal blood flow, thanks to their various mechanisms of perception of chemical and hormonal stimuli.
References
- Blomhoff, R., & Wake, K. (1991). Perisinusoidal stellate cells of the liver: important roles in retinol metabolism and fibrosis. The FASEB Journal, 5, 271–277.
- Dudek, RW (1950). High-Yield Histology (2nd ed.). Philadelphia, Pennsylvania: Lippincott Williams & Wilkins.
- Friedman, SL (2008). Hepatic Stellate Cells: Protean, Multifunctional, and Enigmatic Cells of the Liver. Physiological Reviews, 88, 125-172.
- Gartner, L., & Hiatt, J. (2002). Text Atlas of Histology (2nd ed.). Mexico DF: McGraw-Hill Interamericana Editores.
- Geerts, A. (2001). History, Heterogeneity, Developmental Biology, and Functions of Quiescent Hepatic Stellate Cells. Seminars in Liver Disease, 21 (3), 311–336.
- Johnson, K. (1991). Histology and Cell Biology (2nd ed.). Baltimore, Maryland: The National medical series for independent study.
- Kuehnel, W. (2003). Color Atlas of Cytology, Histology, and Microscopic Anatomy (4th ed.). New York: Thieme.
- Pinzani, M. (1995). Hepatic stellate (ITO) cells: expanding roles for a liver-specific pericyte. Journal of Hepatology, 22, 700–706.
- Puche, JE, Saiman, Y., & Friedman, SL (2013). Hepatic Stellate Cells and Liver Fibrosis. Comprehensive Physiology, 3, 1473–1492.