Hepatic Stellate Cell Culture Models

Rombouts, Krista

doi:10.1016/b978-0-12-800134-9.00002-6

Cited by 6 publications

(9 citation statements)

References 95 publications

(113 reference statements)

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“…Alongside the hepatocytes being the parenchymal cells [2], the liver contains nonparenchymal cells (NPCs) such as Liver Sinusoidal Endothelial Cells (LSECs) [3], Hepatic Stellate Cells (HSCs) [4], Kupffer cells [5], Natural Killer cells [6] and different types of immune cells [7,8]. Each different NPC participates to the liver function and hepatotoxic mechanisms by performing important secondary responses upon hepatocyte damage [9].…”

Section: The Liver and Pathophysiologymentioning

confidence: 99%

“…In a healthy liver the ECM of the normal perisinusoidal space is made up by a well-balanced and specific quantitative and qualitative amount of collagen type I, III, IV, V and VI, fibronectin, laminin and proteoglycans which has been proven to perform a critical role in maintaining the in vivo phenotype of both hepatocytes and NPCs [12][13][14]. Hepatic stellate cells are located in the perisinusoidal space of Disse, HSCs adhere to the endothelial cells and make contact with the hepatocytes [4,15,16]. Upon liver injury, and especially during chronic liver damage, a dynamic and programmed event occur in which HSCs "transdifferentiate" and become activated by a paracrine stimulation followed by autocrine amplification of the fibrogenic signals [15,17].…”

Section: Hepatic Stellate Cells Ecm Producing Cellsmentioning

confidence: 99%

“…In the past decades, several approaches to isolate HSCs have been used that include; density gradient separation, fluorescent cell sorting and explant culture [4]. The method to separate HSCs from other hepatic cells is based on employing an ex-vivo enzymatic digestion of the liver tissue by collagenases, pronases and DNase allowing for the dissociation of the hepatic cells from the surrounding ECM [32][33][34].…”

Section: Hepatic Stellate Cells Ecm Producing Cellsmentioning

confidence: 99%

“…Freshly isolated HSCs are presented with prominent dendritic cytoplasmic processes and retinoids containing lipid droplets. The cells will gradually display a slightly more myofibroblast phenotype marked by heterogeneous retinoid droplet size during the following days in culture [4,35,36]. Henceforth over several decades, many in vitro investigations have demonstrated the remarkable cell plasticity of HSCs that not only reflects various phenotypes but also mirrors different functions.…”

Section: Hepatic Stellate Cells Ecm Producing Cellsmentioning

confidence: 99%

“…Indeed, it has been demonstrated that the behaviour of HSCs is regulated by a 3D ECM [149][150][151][152]. Freshly isolated HSCs showed changes in cell morphology and cellular functions when comparisons were made between 2D plastic cultures and culturing cells in thick matrigel, 3D type I collagen gel or other substrates [4,151]. Henceforth, many different approaches have provided valid information concerning the co-culture of parenchymal cells with HSCs.…”

Section: D In Vitro Hepatic Systemsmentioning

confidence: 99%

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Engineering in vitro models of hepatofibrogenesis

Mazza

Al‐Akkad

Rombouts

2017

Advanced Drug Delivery Reviews

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Chronic liver disease is a major cause of morbidity and mortality worldwide marked by chronic inflammation and fibrosis/scarring, resulting in end-stage liver disease and its complications. Hepatic stellate cells (HSCs) are a dominant contributor to liver fibrosis by producing excessive extracellular matrix (ECM), irrespective of the underlying disease aetiologies, and for many decades research has focused on the development of a number of anti-fibrotic strategies targeting this cell. Despite major improvements in two-dimensional systems (2D) by using a variety of cell culture models of different complexity, an efficient anti-fibrogenic therapy has yet to be developed. The development of well-defined three-dimensional (3D) in vitro models, which mimic ECM structures as found in vivo, have demonstrated the importance of cell-matrix bio-mechanics, the complex interactions between HSCs and hepatocytes and other non-parenchymal cells, and this to improve and promote liver cell-specific functions. Henceforth, refinement of these 3D in vitro models, which reproduce the liver microenvironment, will lead to new objectives and to a possible new era in the search for antifibrogenic compounds.

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Section: The Liver and Pathophysiologymentioning

confidence: 99%

Section: Hepatic Stellate Cells Ecm Producing Cellsmentioning

confidence: 99%

Section: Hepatic Stellate Cells Ecm Producing Cellsmentioning

confidence: 99%

Section: Hepatic Stellate Cells Ecm Producing Cellsmentioning

confidence: 99%

Section: D In Vitro Hepatic Systemsmentioning

confidence: 99%

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Engineering in vitro models of hepatofibrogenesis

Mazza

Al‐Akkad

Rombouts

2017

Advanced Drug Delivery Reviews

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Determination and Characterization of Tetraspanin-Associated Phosphoinositide-4 Kinases in Primary and Neoplastic Liver Cells

Rombouts

Carloni

2016

Methods in Molecular Biology

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Therapeutic Targeting of Hepatic Macrophages

Nijland

Bansal²

2020

Curr. Tissue Microenviron. Rep.

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Purpose of Review This review outlines the current knowledge about hepatic macrophages and provides an overview of therapeutic approaches to target hepatic macrophages for the treatment of liver diseases. Recent Findings In recent years, it has been increasingly recognized that hepatic macrophages (resident macrophages, Kupffer cells, or circulating bone marrow monocyte-derived macrophages) are implicated in liver homeostasis as well as in disease progression and resolution. More recently, different populations of hepatic macrophages with distinct phenotypes and functions have been identified that have shown to play distinct roles in the pathogenesis of various acute and chronic liver diseases. The understanding of the role of hepatic macrophages in initiation, progression, and resolution of liver diseases has given rise to the development of therapeutics that can target different phenotypes of hepatic macrophages. Innovative strategies comprises of microRNA (miRNA), small interfering RNA (siRNA), therapeutic proteins, and small-molecule inhibitors. Summary Evidence from recent in vitro and in vivo studies support the fact that hepatic macrophages can be efficiently targeted using miRNA/siRNA-based approaches, protein-based approaches, and small-molecule inhibitors for the treatment of liver diseases. However, more in-depth understanding underlying the roles of distinct macrophage phenotypes in different liver diseases is required for the translation of novel targeted therapeutics to the clinic. Keywords Hepatic macrophages. Targeted therapeutics. Liver diseases. Monocytes. Kupffer cells This article is part of the Topical Collection on Chronic Liver Disease

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Hepatic Stellate Cell Culture Models

Cited by 6 publications

References 95 publications

Engineering in vitro models of hepatofibrogenesis

Engineering in vitro models of hepatofibrogenesis

Determination and Characterization of Tetraspanin-Associated Phosphoinositide-4 Kinases in Primary and Neoplastic Liver Cells

Therapeutic Targeting of Hepatic Macrophages

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