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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.<ref>{{cite journal |author=Geerts A |year=2001 |title=History, heterogeneity, developmental biology, and functions of quiescent hepatic stellate cells |journal=Semin Liver Dis |volume=21 |issue=3 |pages=311–35 |PMID=11586463 |doi=10.1055/s-2001-17550}}</ref> Each cell has several long protrusions that extend from the cell body and wrap around the sinusoids. The [[lipid]] droplets in the cell body store [[retinol|vitamin A]] as [[retinol]] [[ester]]. 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 [[Natural Killer T cell|NKT cells]].<ref name="Kaufmann">{{cite journal | pmid = 17239632 | doi=10.1016/j.immuni.2006.11.011 | volume=26 | issue=1 | title=Ito cells are liver-resident antigen-presenting cells for activating T cell responses |date=January 2007 |vauthors=Winau F, Hegasy G, Weiskirchen R, etal | pages=117–29 | journal=Immunity}}</ref>
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.<ref>{{cite journal |author=Geerts A |year=2001 |title=History, heterogeneity, developmental biology, and functions of quiescent hepatic stellate cells |journal=Semin Liver Dis |volume=21 |issue=3 |pages=311–35 |PMID=11586463 |doi=10.1055/s-2001-17550}}</ref> Each cell has several long protrusions that extend from the cell body and wrap around the sinusoids. The [[lipid]] droplets in the cell body store [[retinol|vitamin A]] as [[retinol]] [[ester]]. 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 [[Natural Killer T cell|NKT cells]].<ref name="Kaufmann">{{cite journal | pmid = 17239632 | doi=10.1016/j.immuni.2006.11.011 | volume=26 | issue=1 | title=Ito cells are liver-resident antigen-presenting cells for activating T cell responses |date=January 2007 |vauthors=Winau F, Hegasy G, Weiskirchen R, etal | pages=117–29 | journal=Immunity}}</ref>


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 state of the stellate cell is the main source of extracellular matrix production in liver injury.<ref>{{Cite journal|last=Eng|first=F. J.|last2=Friedman|first2=S. L.|date=July 2000|title=Fibrogenesis I. New insights into hepatic stellate cell activation: the simple becomes complex|journal=American Journal of Physiology. Gastrointestinal and Liver Physiology|volume=279|issue=1|pages=G7–G11|issn=0193-1857|pmid=10898741|doi=10.1152/ajpgi.2000.279.1.g7}}</ref> This attribute makes it a key factor in the pathophysiology of the liver. The amount of stored vitamin A decreases progressively in liver injury.<ref name="Stanciu" /> The activated stellate cell is also responsible for secreting [[collagen]] scar tissue, which can lead to [[cirrhosis]].<ref>{{cite web|url=http://stemcellthailand.org/therapies/renal-failure-kidney-disease/|title=mesenchymal stem cell treatments for ischemic kidney disease | accessdate=2012-08-07}}</ref> More recent 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 [[Retinoblastoma protein|Rb]]–hallmarks of cellular senescence. Senescent hepatic stellate cells have been demonstrated to limit liver fibrosis by activating interactions with [[Natural killer cell|NK cells]].<ref name="Krizhanovsky">{{cite journal | pmid = 18724938 | doi=10.1016/j.cell.2008.06.049 | volume=134 | issue=4 | title=Senescence of activated stellate cells limits liver fibrosis | pmc=3073300 |date=August 2008 |vauthors=Krizhanovsky V, Yon M, Dickins RA, etal | pages=657–67 | journal=Cell}}</ref><ref>{{Cite journal|last=Fasbender|first=Frank|last2=Widera|first2=Agata|last3=Hengstler|first3=Jan G.|last4=Watzl|first4=Carsten|date=2016-01-29|title=Natural Killer Cells and Liver Fibrosis|journal=Frontiers in Immunology|volume=7|doi=10.3389/fimmu.2016.00019|issn=1664-3224|pmc=4731511|pmid=26858722}}</ref>
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 state of the stellate cell is the main source of extracellular matrix production in liver injury.<ref>{{Cite journal|last=Eng|first=F. J.|last2=Friedman|first2=S. L.|date=July 2000|title=Fibrogenesis I. New insights into hepatic stellate cell activation: the simple becomes complex|journal=American Journal of Physiology. Gastrointestinal and Liver Physiology|volume=279|issue=1|pages=G7–G11|issn=0193-1857|pmid=10898741|doi=10.1152/ajpgi.2000.279.1.g7}}</ref> This attribute makes it a key factor in the pathophysiology of the liver. The amount of stored vitamin A decreases progressively in liver injury.<ref name="Stanciu" /> The activated stellate cell is also responsible for secreting [[collagen]] scar tissue, which can lead to [[cirrhosis]].<ref>{{cite web|url=http://stemcellthailand.org/therapies/renal-failure-kidney-disease/|title=mesenchymal stem cell treatments for ischemic kidney disease | accessdate=2012-08-07}}</ref> More recent 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 [[Retinoblastoma protein|Rb]]–hallmarks of cellular senescence. Senescent hepatic stellate cells have been demonstrated to limit liver fibrosis by activating interactions with [[Natural killer cell|NK cells]].<ref name="Krizhanovsky">{{cite journal | pmid = 18724938 | doi=10.1016/j.cell.2008.06.049 | volume=134 | issue=4 | title=Senescence of activated stellate cells limits liver fibrosis | pmc=3073300 |date=August 2008 |vauthors=Krizhanovsky V, Yon M, Dickins RA, etal | pages=657–67 | journal=Cell}}</ref><ref>{{Cite journal|last=Fasbender|first=Frank|last2=Widera|first2=Agata|last3=Hengstler|first3=Jan G.|last4=Watzl|first4=Carsten|date=2016-01-29|title=Natural Killer Cells and Liver Fibrosis|journal=Frontiers in Immunology|volume=7|doi=10.3389/fimmu.2016.00019|issn=1664-3224|pmc=4731511|pmid=26858722}}</ref>

===Drug under investigation===
The experimental drug PBI-4050 which reduces stellate cell activation and liver fibrosis through modulation of intracellular ATP levels and LKB1-AMPK-mTOR pathway is under investigation by the Canadian biotechnology firm Prometic. As of August 2018, it remains a promising drug targeting multiple type of fibrosis entering phase 3 clinical trials.<ref>http://jpet.aspetjournals.org/content/early/2018/08/09/jpet.118.250068</ref>.


==History==
==History==

Revision as of 18:28, 11 August 2018

Not to be confused with Hematopoietic stem cells, which also use the acronym HSC.
Hepatic stellate cell
Schematic presentation of hepatic stellate cells (HSC) located in the vicinity of adjacent hepatocytes (PC) beneath the sinusoidal endothelial cells (EC). S – liver sinusoids; KC – Kupffer cells. Down left shows cultured HSC at light-microscopy, whereas at down right electron microscopy (EM) illustrates numerous fat vacuoles (L) in a HSC, in which retinoids are stored.
Basic liver structure
Details
Locationperisinusoidal space of liver
Identifiers
Latincellula perisinusoidalis; cellula accumulans adipem
MeSHD055166
THH3.04.05.0.00013
Anatomical terms of microanatomy

Hepatic stellate cells (here 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.

Structure

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 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.

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.[4] Each cell has several long protrusions that extend from the cell body and wrap around the sinusoids. The lipid droplets in the cell body store vitamin A as retinol ester. 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.[5]

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 state of the stellate cell is the main source of extracellular matrix production in liver injury.[6] 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 is also responsible for secreting collagen scar tissue, which can lead to cirrhosis.[7] More recent 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.[8][9]

History

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.[10][11]

See also

References

  1. ^ a b "New data about ITO cells". Rev Med Chir Soc Med Nat Iasi. 107 (2): 235–239. 2002. PMID 12638266. {{cite journal}}: Unknown parameter |authors= ignored (help)
  2. ^ Motoyama H (Feb 2014). "Cytoglobin is expressed in hepatic stellate cells, but not in myofibroblasts, in normal and fibrotic human liver". Lab Invest. 94 (2): 192–207. doi:10.1038/labinvest.2013.135. PMID 24296877.
  3. ^ "Expression of reelin in hepatic stellate cells and during hepatic tissue repair: a novel marker for the differentiation of HSC from other liver myofibroblasts". J Hepatol. 36 (5): 607–13. 2002. doi:10.1016/S0168-8278(02)00050-8. PMID 11983443. {{cite journal}}: Unknown parameter |authors= ignored (help)
  4. ^ Geerts A (2001). "History, heterogeneity, developmental biology, and functions of quiescent hepatic stellate cells". Semin Liver Dis. 21 (3): 311–35. doi:10.1055/s-2001-17550. PMID 11586463.
  5. ^ Winau F, Hegasy G, Weiskirchen R, et al. (January 2007). "Ito cells are liver-resident antigen-presenting cells for activating T cell responses". Immunity. 26 (1): 117–29. doi:10.1016/j.immuni.2006.11.011. PMID 17239632.
  6. ^ Eng, F. J.; Friedman, S. L. (July 2000). "Fibrogenesis I. New insights into hepatic stellate cell activation: the simple becomes complex". American Journal of Physiology. Gastrointestinal and Liver Physiology. 279 (1): G7–G11. doi:10.1152/ajpgi.2000.279.1.g7. ISSN 0193-1857. PMID 10898741.
  7. ^ "mesenchymal stem cell treatments for ischemic kidney disease". Retrieved 2012-08-07.
  8. ^ Krizhanovsky V, Yon M, Dickins RA, et al. (August 2008). "Senescence of activated stellate cells limits liver fibrosis". Cell. 134 (4): 657–67. doi:10.1016/j.cell.2008.06.049. PMC 3073300. PMID 18724938.
  9. ^ Fasbender, Frank; Widera, Agata; Hengstler, Jan G.; Watzl, Carsten (2016-01-29). "Natural Killer Cells and Liver Fibrosis". Frontiers in Immunology. 7. doi:10.3389/fimmu.2016.00019. ISSN 1664-3224. PMC 4731511. PMID 26858722.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  10. ^ "Professor Toshio Ito: a clairvoyant in pericyte biology" (PDF). The Keio Journal of Medicine. 50 (2): 66–71. 2001. doi:10.2302/kjm.50.66. PMID 11450594. {{cite journal}}: Unknown parameter |authors= ignored (help)
  11. ^ Friedman, Scott L. (2008-01-01). "Hepatic Stellate Cells: Protean, Multifunctional, and Enigmatic Cells of the Liver". Physiological Reviews. 88 (1): 125–172. doi:10.1152/physrev.00013.2007. ISSN 0031-9333. PMC 2888531. PMID 18195085.
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