The Hepatic Stellate Cell
Massimo Pinzani
Search for more papers by this authorMassimo Pinzani
Search for more papers by this authorJuan Rodés MD
Director General, Hospital Clinic; Professor of Medicine, University of Barcelona, Barcelona, Spain
Search for more papers by this authorJean-Pierre Benhamou MD
Professor of Hepatology, Université Denis Diderot Paris 7, Assistance Publique — Hôpitaux de Paris and Inserm U773, Service d'Hépatologie, Hôpital Beaujon, Clichy, France
Search for more papers by this authorAndres T. Blei MD
Professor of Medicine and Surgery, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA
Search for more papers by this authorJürg Reichen MD
Professor of Medicine, University of Bern; Chief of Hepatology, University Hospital, Bern, Switzerland
Search for more papers by this authorMario Rizzetto MD
Professor of Gastroenterology, University of Turin, Turin, Italy
Search for more papers by this authorSummary
This chapter contains section titled:
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Historical Notes and Nomenclature
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Anatomy and Ultrastructure
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Retinoid Storage and Metabolism
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Intralobular Heterogeneity of HSC
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Isolation and Culture of HSC
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Identification of HSC and Related Hepatic Fibrogenic Cells
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The Embryonic Origin of HSC
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Rodent, Human and HSC Lines: Differences and Similarities
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Extrahepatic HSC and the ‘Stellate Cell System’
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HSC and Extracellular Matrix Homeostasis
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HSC as Liver-Specific Pericytes
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References
References
-
Kupffer K
(1876)
Uber Sternzellen der Leber. Briefliche Mitteilung an Professor Waldeyer.
Arch Mikr Anat
12,
353–358.
10.1007/BF02933897 Google Scholar
- Zimmerman K (1928) Uber das Verhaltniss der ‘Kupfferschen Sternzellen’ zum Endothel der Leberkapillaren beim Menschen. Ztsch Mikr Anat Forsch 14, 528–548.
- Ito T, Nemoto M (1952) Uber die Kupfferschen Sternzellen und die ‘Fettspeicherungzellen’ (fat storing cells) in der Blutkapillarenwand der menschlichen Leber. Okajima Folia Anat Jpn 24, 243–258.
- Wake K (1980) Perisinusoidal stellate cells (fat-storing cells, interstitial cells, lipocytes), their related structure in and around the liver sinusoids, and vitamin A-storing cells in extrahepatic organs. Int Rev Cytol 66, 303–353.
- McGee JO, Patrick RS (1972) The role of perisinusoidal cells in hepatic fibrogenesis. An electron microscopic study of acute carbon tetrachloride liver injury. Lab Invest 26, 429–440.
- McGee JO, Patrick RS (1972) The role of perisinusoidal cells in experimental hepatic fibrogenesis. J Pathol 106 (1), vi.
- Kent G, Gay S, Inouye T et al. (1976) Vitamin A-containing lipocytes and formation of type III collagen in liver injury. Proc Natl Acad Sci USA 73, 3719–3722.
- Ueno T, Bioulac-Sage P, Balabaud C et al. (2004) Innervation of the sinusoidal wall: regulation of the sinusoidal diameter. Anat Rec A Discov Mol Cell Evol Biol 280, 868–873.
- Cassiman D, Roskams T (2002) Beauty is in the eye of the beholder: emerging concepts and pitfalls in hepatic stellate cell research. J Hepatol 37, 527–535.
- Oben JA, Diehl AM (2004) Sympathetic nervous system regulation of liver repair. Anat Rec A Discov Mol Cell Evol Biol 280, 874–883.
- Letter to the editor (1996) Hepatic stellate cell nomenclature (letter). Hepatology 23, 193.
-
Wake K
(1988)
Liver perivascular cells revealed by gold and silver impregnation methods and electron microscopy. In:
P Motta (ed.)
Biopathology of the Liver, an Ultrastructural Approach.
Dordrecht:
Kluwer,
pp. 23–26.
10.1007/978-94-009-1239-7_3 Google Scholar
-
Wake K
(1999)
Hepatic stellate cells. In:
K Tanikawa,
T Ueno (eds)
Liver Diseases and Hepatic Sinusoidal Cells.
Tokyo:
Springer-Verlag,
pp. 56–65.
10.1007/978-4-431-67935-6_3 Google Scholar
- Wake K (1995) Structure of the sinusoidal wall in the liver. In: E Wisse, DL Knook, K Wake (eds) Cells of the Hepatic Sinusoid. Leiden: The Kupffer Cell Foundation, pp. 241–246.
- Wake K, Motomatsu K, Ekataksin W (1991) Postnatal development of the perisinusoidal stellate cells in the rat liver. In: E Wisse, DL Knook, RS McCuskey (eds) Cells of the Hepatic Sinusoid. Leiden: The Kupffer Cell Foundation, pp. 269–275.
- Gressner AM, Lofti S, Gressner G et al. (1992) Identification and partial characterization of a hepatocyte-derived factor promoting proliferation of cultured fat-storing cells (parasinusoidal lipocytes). Hepatology 16, 1250–1266.
- Wanson JC, Mosselmans R (1980) Coculture of adult rat hepatocytes and sinusoidal cells: a new experimental model for the study of ultra-structural and functional properties of liver cells. In: H Popper, L Bianchi, F Gudat et al. (eds) Communications of Liver Cells. Lancaster: MTP Press, pp. 239–251.
- Sztark F, Dubroca J, Latry P et al. (1986) Perisinusoidal cells in patients with normal liver histology. A morphometric study. J Hepatol 2, 358–369.
- Blomhoff R, Wake K (1991) Perisinusoidal stellate cells of the liver: important roles in retinol metabolism and fibrosis. FASEB J 5, 271–277.
- Blomhoff R, Berg T, Norum KR (1988) Transfer of retinol from parenchymal to stellate cells in liver is mediated by retinol-binding protein. Proc Natl Acad Sci USA 85, 3455–3458.
- Blomhoff R, Rasmussen M, Nilsson A et al. (1985) Hepatic retinol metabolism. Distribution of retinoids, enzymes, and binding proteins in isolated rat liver cells. J Biol Chem 260, 13560–13565.
- Uchio K, Tuchweber B, Manabe N et al. (2002) Cellular retinol-binding protein-1 expression and modulation during in vivo and in vitro myofibroblastic differentiation of rat hepatic stellate cells and portal fibroblasts. Lab Invest 82, 619–628.
- Matsuura T, Nagamori S, Fujise K et al. (1989) Retinol transport in cultured fat-storing cells of rat liver. Quantitative analysis by anchored cell analysis and sorting system. Lab Invest 61, 107–115.
- Pinzani M, Gentilini P, Abboud HE (1992) Phenotypical modulation of liver fat-storing cells by retinoids. Influence on unstimulated and growth factor-induced cell proliferation. J Hepatol 14, 211–220.
- Moriwaki K, Blaner WS, Piantedosi R et al. (1988) Effects of dietary retinoids and triglyceride on the lipid composition of rat liver stellate cells and stellate cell lipid droplets. J Lipid Res 29, 1523–1534.
- Blaner WS, Hendriks HF, Brouwer A et al. (1985) Retinoids, retinoid binding proteins and retinyl palmitate hydrolase distributions in different types of rat liver cells. J Lipid Res 26, 1241–1251.
- Friedman SL, Wei S, Blaner WS (1993) Retinol release by activated rat hepatic lipocytes: regulation by Kupffer cell-conditioned medium and PDGF. Am J Physiol 264, G947–952.
- Blomhoff R, Norum KR, Berg T (1985) Hepatic uptake of [3H]retinol bound to the serum retinol binding protein involves both parenchymal and perisinusoidal stellate cells. J Biol Chem 260, 13571–13575.
- Weiner FR, Blaner WS, Czaja MJ et al. (1992) Ito cell expression of a nuclear retinoic acid receptor. Hepatology 15, 336–342.
- Mangelsdorf DJ, Thummel C, Beato M et al. (1995) The nuclear receptor superfamily: the second decade. Cell 83, 835–839.
- Ulven SM, Natarajan V, Holven KB et al. (1998) Expression of retinoic acid receptor and retinoid X receptor subtypes in rat liver cells: implications for retinoid signalling in parenchymal, endothelial, Kupffer and stellate cells. Eur J Cell Biol 77, 111–116.
- Ballardini G, Groff P, de Giorgi Badiali L et al. (1994) Ito cell heterogeneity: desmin-negative Ito cells in normal rat liver. Hepatology 19, 440–446.
- Zou Z, Ekataksin W, Wake K (1998) Zonal and regional differences identified from precision mapping of vitamin A-storing lipid droplets of the hepatic stellate cells in pig liver: a novel concept of addressing the intralobular area of heterogeneity. Hepatology 27, 1098–1108.
- Higashi N, Senoo H (2003) Distribution of vitamin A-storing lipid droplets in hepatic stellate cells in liver lobules — a comparative study. Anat Rec A Discov Mol Cell Evol Biol 271, 240–248.
- Knook DL, Seffelaar AM, De Leuw AM (1982) Fat-storing cells of rat liver. Their isolation and purification. Exp Cell Res 139, 468–471.
- Friedman SL, Roll FJ (1987) Isolation and culture of hepatic lipocytes, Kupffer cells and sinusoidal endothelial cells by density gradient cen-trifugation with stractan. Anal Biochem 161, 207–218.
- Mantovaara T, Norlinder H, Pertof H (1990) Isolation of the perisinusoidal vitamin A storing cells from rat liver on Ca2+ immobilized glass surfaces. Exp Cell Res 187, 170–173.
- Pinzani M, Abboud HE, Gesualdo L et al. (1992) Regulation of macrophage-colony stimulating factor in liver fat-storing cells by peptide growth factors. Am J Physiol Cell Physiol 262, C876–C881.
- Friedman SL, Rockey DC, McGuire RF et al. (1992) Isolated hepatic lipocytes and Kupffer cells from normal human liver: morphological and functional characteristics in primary culture. Hepatology 15, 234–243.
- Casini A, Pinzani M, Milani S et al. (1993) Regulation of transforming growth factor-?1 in human fat-storing cells. Gastroenterology 105, 245–253.
- Maher JJ, Bissell DM, Friedman SL et al. (1988) Collagen measured in primary cultures of normal rat hepatocytes derives from lipocytes within the monolayer. J Clin Invest 82, 450–459.
- Geerts A, Niki T, Hellemans K et al. (1998) Purification of rat hepatic stellate cells by side scatter-activated cell sorting. Hepatology 27, 590–598.
- Bioulac-Sage P, Balabaud C (1992) Proliferation and phenotypic expression of perisinusoidal cells. J Hepatol 15, 284–287.
- Pinzani M, Gesualdo L, Sabbah GM et al. (1989) Effects of platelet-derived growth factor and other polypeptide mitogens on DNA synthesis and growth of cultured rat liver fat-storing cells. J Clin Invest 84, 1786–1793.
- Geerts A (2001) History, heterogeneity, developmental biology, and functions of quiescent hepatic stellate cells. Semin Liver Dis 21, 311–335.
- Ramadori G, Veit T, Schwogler S et al. (1990) Expression of the gene of the alpha-smooth muscle-actin isoform in rat liver and in rat fat-storing (Ito) cells. Virchows Arch B Cell Pathol Incl Mol Pathol 59, 349–357.
- Rockey DC, Boyles JK, Gabbiani G et al. (1992) Rat hepatic lipocytes express smooth muscle actin upon activation in vivo and in culture. J Submicrosc Cytol Pathol 24, 193–203.
- Pinzani M, Rombouts K (2004) Liver fibrosis: from the bench to clinical targets. Dig Liver Dis 36, 231–242.
- Cassiman D, Libbrecht L, Desmet V et al. (2002) Hepatic stellate cell/myofibroblast subpopulations in fibrotic human and rat livers. J Hepatol 36, 200–209.
- Cassiman D, van Pelt J, De Vos R et al. (1999) Synaptophysin: a novel marker for human and rat hepatic stellate cells. Am J Pathol 155, 1831–1839.
- Cassiman D, Denef C, Desmet V et al. (2001) Human and rat hepatic stellate cells express neurotrophins and neurotrophin receptors. Hepatology 33, 148–158.
- Geerts A (2004) On the origin of stellate cells: mesodermal, endoder-mal or neuroectodermal? J Hepatol 40, 331–334.
- Kiassov AP, Van Eyken P, van Pelt JF et al. (1995) Desmin expressing nonhematopoietic liver cells during rat liver development: an immunohistochemical and morphometric study. Differentiation 59, 253–258.
- Forbes SJ, Russo FP, Rey V et al. (2004) A significant proportion of myofibroblasts are of bone marrow origin in human liver fibrosis. Gastroenterology 126, 955–963.
- Baba S, Fujii H, Hirose T et al. (2004) Commitment of bone marrow cells to hepatic stellate cells in mouse. J Hepatol 40, 255–260.
- Suskind DL, Muench MO (2004) Searching for common stem cells of the hepatic and hematopoietic systems in the human fetal liver: CD34+ cytokeratin 7/8+ cells express markers for stellate cells. J Hepatol 40, 261–268.
- Saile B, Matthes N, Neubauer K et al. (2002) Rat liver myofibroblasts and hepatic stellate cells differ in CD95-mediated apoptosis and response to TNF-alpha. Am J Physiol Gastrointest Liver Physiol 283, G435–G444.
- Xu L, Hui AY, Albanis E et al. (2005) Human hepatic stellate cell lines, LX-1 and LX-2: new tools for analysis of hepatic fibrosis. Gut 54, 142–151.
- Shibata N, Watanabe T, Okitsu T et al. (2003) Establishment of an immortalized human hepatic stellate cell line to develop antifibrotic therapies. Cell Transplant 12, 499–507.
- Schnabl B, Choi YH, Olsen JC et al. (2002) Immortal activated human hepatic stellate cells generated by ectopic telomerase expression. Lab Invest 82, 323–333.
- Apte MV, Wilson JS (2004) Mechanisms of pancreatic fibrosis. Dig Dis 22, 273–279.
- Milani S, Herbst H, Schuppan D et al. (1989) In situ hybridization for procollagen types I, III and IV mRNA in normal and fibrotic rat liver: evidence for predominant expression in nonparenchymal liver cells. Hepatology 10, 84–92.
- Milani S, Herbst H, Schuppan D et al. (1989) Cellular localization of laminin gene transcripts in normal and fibrotic human liver. Am J Pathol 134, 1175–1182.
- Maher JJ, McGuire RF (1990) Extracellular matrix gene expression increases preferentially in rat lipocytes and sinusoidal endothelial cells during hepatic fibrosis in vivo. J Clin Invest 86, 1641–1648.
- Milani S, Herbst H, Schuppan D et al. (1994) Differential expression of matrix-metalloproteinase-1 and -2 genes in normal and fibrotic human liver. Am J Pathol 144, 528–537.
- Pinzani M, Gentilini P (1999) Biology of hepatic stellate cells and their possible relevance in the pathogenesis of portal hypertension in cirrhosis. Semin Liver Dis 19, 397–410.
- Pinzani M, Failli P, Ruocco C et al. (1992) Fat-storing cells as liver-specific pericytes. Spatial dynamics of agonist-stimulated intracellular calcium transients. J Clin Invest 90, 642–646.
- Ekataksin W, Kaneda K (1999) Liver microvascular architecture: an insight into the pathophysiology of portal hypertension. Semin Liver Dis 19, 359–382.
- Zhang JX, Pegoli W Jr,, Clemens MG (1994) Endothelin-1 induces direct constriction of hepatic sinusoids. Am J Physiol 266, G624–632.
- Zhang JX, Bauer M, Clemens MG (1995) Vessel- and target cell-specific actions of endothelin-1 and endothelin-3 in rat liver. Am J Physiol 269, G269–277.
- Thimgan MS, Yee HF Jr (1999) Quantitation of rat hepatic stellate cell contraction: stellate cells' contribution to sinusoidal tone. Am J Physiol 277, G137–G143.
- Wake K, Sato T (1993) Intralobalar heterogeneity of perisinusoidal stellate cells in porcine liver. Cell Tissue Res 273, 227–237.
- Wake K (1977) Chapter in: F Vidal-Vanaclocha (ed.) Functional Heterogeneity of Liver Tissue. Austin, TX: RG Landes Co.
- Pinzani M (1995) Novel insights into the biology and physiology of the Ito cell. Pharmac Ther 66, 387–412.