The Niche of Stellate Cells Within Rat Liver

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 beta-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 M, and parenchymal cells, which synthesize beta-catenin-dependent Wnt ligands and Jagged 1. 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. (HEPATOLOGY 2009;50:1617-1624.)