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      The hepatic stellate (Ito) cell: its role in human liver disease

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      Virchows Archiv
      Springer Science and Business Media LLC

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          Abstract

          The hepatic stellate (Ito) cell lies within the space of Disse and has a variety of functions. Stellate cells store vitamin A in characteristic lipid droplets. In the normal human liver, the cells can be identified by the presence of these lipid droplets; in addition, many stellate cells in the normal liver express alpha-smooth muscle actin. In acute liver injury, there is an expansion of the stellate cell population with increased alpha-smooth muscle actin expression; stellate cells appear to play a role in extracellular matrix remodelling after recovery from injury. In chronic liver injury, the stellate cell differentiates into a myofibroblast-like cell with marked expression of alpha-smooth muscle actin and occasional expression of desmin. Myofibroblast-like cells have a high fibrogenic capacity in the chronically diseased liver and are also involved in matrix degradation. In vitamin A intoxication, hypertrophy and proliferation of the stellate and myofibroblast-like cells may lead to non-cirrhotic portal hypertension, fibrosis and cirrhosis. In liver tumours, myofibroblast-like cells are involved in the capsule formation around the tumour and in the production of extracellular matrix within it. The transition of stellate cells into myofibroblast-like cells is regulated by an intricate network of intercellular communication between stellate cells and activated Kupffer cells, damaged hepatocytes, platelets, endothelial and inflammatory cells, involving cytokines and nonpeptide mediators such as reactive oxygen species, eicosanoids and acetaldehyde. The findings suggest that the stellate cell plays an active role in a number of human liver diseases, with a particular reactivity pattern in fibrotic liver disorders.

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          Most cited references94

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          Seminars in medicine of the Beth Israel Hospital, Boston. The cellular basis of hepatic fibrosis. Mechanisms and treatment strategies.

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              Isolated hepatic lipocytes and Kupffer cells from normal human liver: morphological and functional characteristics in primary culture.

              The development of techniques for isolating hepatic lipocytes (Ito, stellate or fat-storing cells) from rodents has been instrumental in defining their role in hepatic vitamin A storage and fibrogenesis. In this study, we developed a method for the purification of lipocytes and Kupffer cell from wedge sections of normal human liver and examined their properties in primary culture. Sections of donor liver (400 to 600 gm) harvested but not used for transplantation were perfused in situ with University of Wisconsin solution and used for lipocyte isolation within 48 hr. Cells were isolated by catheter perfusion of the wedge through several large vessels with L-15 salts, Pronase and collagenase, followed by Larex density gradient centrifugation. Lipocytes were plated on either uncoated plastic or a basement membrane-like gel. Lipocyte and Kupffer cell yields were 2.3 +/- 0.6 x 10(5) and 8.6 +/- 1.4 x 10(5) cells, respectively, per gram of liver (n = 5). Lipocyte purity was 91% as assessed by vitamin A autofluorescence, and Kupffer cell purity was 83% as determined by uptake of fluorescinated staphylococci. Lipocytes cultured on the plastic spread within 48 to 72 hr, displaying slightly more heterogeneous retinoid droplet size than comparable rat cells; on a basement-membrane gel, the cells remained aggregated and spherical with occasional spindlelike extensions. Lipocytes on plastic expressed procollagens I and III, collagen IV and laminin by immunocytochemistry, and types I, III and IV procollagen messenger RNAs by RNAse protection. Northern blot and polymerase chain reaction, respectively. Transmission electron microscopy of lipocytes at 7 days demonstrated a prominent rough endoplasmic reticulum and contractile filaments. Scanning electron microscopy revealed a smooth cell surface with perinuclear droplets beneath the cell membrane. With continued primary culture on plastic (more than 7 days), cells appeared "activated" (i.e., increased spreading and diminished retinoid droplets) and began proliferating as assessed by nuclear autoradiography and [3H]thymidine incorporation. Kupffer cells observed by scanning electron microscopy in early primary culture displayed prominent membrane ruffling and lamellipodia. In summary, we have established a reproducible method for the isolation and primary culture of human lipocytes and Kupffer cells.
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                Author and article information

                Journal
                Virchows Archiv
                Virchows Archiv
                Springer Science and Business Media LLC
                0945-6317
                1432-2307
                March 1997
                March 1997
                : 430
                : 3
                : 195-207
                Article
                10.1007/BF01324802
                9099976
                078e01e9-b0ec-4698-bef8-12de86e33bed
                © 1997

                http://www.springer.com/tdm

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