Hepatic stellate cells (HSCs) reside between the basolateral surface of the hepatocytes and the abluminal surface of the sinusoidal endothelial cells in the perisinusoidal space (space of Disse). Stellate cell roles include vitamin A storage and modulation of hepatic microcirculation in response to endothelin signaling. In adult liver, quiescent HSCs are characterized by the expression of desmin, storage of vitamin A, and extensive dendrite-like processes along the sinusoid.
The origin of hepatic stellate cells hasn't been fully elucidated, with evidence of endodermal, neural crest, or mesenchymal origin. Direct lineage tracing experiments performed in avian embryos, demonstrated that mesothelial cells derived from the proepicardium and septum transversum mesenchyme could give rise to both endothelial and stellate cells within the hepatic sinusoids. Recent studies in human and in mouse support these findings.
Upon injury, cytokines and reactive oxygen species released by injured hepatocytes, Kupffer cells, and HSCs trigger HSC activation. Activated HSCs lose vitamin A, take on a myofibroblastic phenotype expressing alpha-SMA, and synthesize proinflammatory cytokines and large quantities of extracellular matrix proteins. Desmin is uniformly expressed in rat HSCs, but is barely expressed or often absent in human HSCs. About 70–80% of quiescent rodent HSCs express GFAP, while quiescent human HSCs do not.
Multiple AncestorsSingle AncestorNo DescendantsDevelops fromPart of Parent