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The niche of stellate cells within rat liver
Author(s) -
Sawitza Iris,
Kordes Claus,
Reister Sven,
Häussinger Dieter
Publication year - 2009
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.23184
Subject(s) - hepatic stellate cell , microbiology and biotechnology , biology , perisinusoidal space , stem cell , liver cytology , wnt signaling pathway , progenitor cell , paracrine signalling , extracellular matrix , basal lamina , stromal cell , endothelial stem cell , anatomy , signal transduction , receptor , cancer research , endocrinology , hepatocyte , biochemistry , liver metabolism , ultrastructure , in vitro
It is well‐accepted that hepatic stellate cells (HSCs) can develop into myofibroblast‐like cells that synthesize extracellular matrix proteins and contribute to liver fibrosis. Recently, molecular markers of stem/progenitor cells were discovered in HSCs of rats. Moreover, the cells displayed the capacity to differentiate and to participate in liver regeneration. In addition, stellate cells possess signaling pathways important for maintenance of stemness and cell differentiation such as hedgehog and β‐catenin–dependent Wnt signaling. All these properties are congruently found in stem/progenitor cells. Stem cells require a special microenvironment, the so‐called stem cell niche, to maintain their characteristics. Thus, we investigated if the space of Disse, where stellate cells reside in the liver innervated by the sympathetic nervous system and surrounded by sinusoidal endothelial cells and parenchymal cells, exhibits similarities with known stem cell niches. The present study describes the niche of stellate cells within the liver of rats that is composed of sinusoidal endothelial cells, which release stromal cell–derived factor‐1 to attract stellate cells via the cysteine‐X‐cysteine receptor 4, basal lamina proteins (laminin and collagen type IV), and parenchymal cells, which synthesize β‐catenin–dependent Wnt ligands and Jagged1. Conclusion: The space of Disse shows analogies to typical stem cell niches comprising of basal lamina components, sympathetic innervation, and adjacent cells that constitute a milieu by paracrine factors and direct physical interactions to retain HSCs at this site and to influence their cellular fate. The space of Disse serves as a niche of stellate cells, which is a novel function of this unique organ structure. (H EPATOLOGY 2009.)