Hepatic stellate cells (HSCs) — also called interstitial cells, fat-storing cells, Vitamin A-storing cells, or Ito cells — are perisinusoidal cells distributed throughout the liver, located in the space of Disse between the hepatocytes and sinusoidal endothelial cells. The stellate cells arise embryologically from the septum transversum mesenchyme from precursor cells that invade the liver parenchyma from the hepatic capsule. In the normal adult liver, these important cells store retinoids as retinyl palmitate in cytoplasmic lipid droplets and are pivotal in the regulation of retinoid homeostasis. Other functions ascribed to hepatic stellate cells include vasoregulation (through interactions with endothelial cells), extracellular matrix homeostasis, immune regulation, drug detoxification, and production of mitogens and morphogens (such as hepatocyte growth factor) that serve to preserve and/or restore hepatocyte mass.
Under physiological conditions, HSCs exhibit a quiescent phenotype (qHSCs). They express neural markers, such as GFAP, synemin, synaptophysin, and nerve growth factor receptor p75 and store vitamin A in lipid droplets. In response to liver injury, such as chronic exposure to certain drugs or chemicals, steatosis, and/or persistent inflammation, qHSCs decrease vitamin A storage and peroxisome proliferator-activated receptor (PPAR) expression, and activate into collagen type I and αSMA expressing myofibroblasts (aHSCs). Persistent activation of HSCs and intrahepatic presence of myofibroblasts leads to fibrosis, portal hypertension, and cirrhosis, thus aHSCs are the primary target for anti-fibrosis therapies. Active areas of research involving stellate cells are broad, and include mechanisms of activation, fibrosis and resolution of fibrosis, inflammation, regeneration, and the development of hepatocellular cancer.
In vitro monolayer culture of hepatic stellate cells typically results in the development of a culture-activated phenotype, with progressive increases in expression of αSMA and loss of phenotypic features associated with quiescence, including lipid droplets and expression of GFAP. However, study results have suggested that culture-activated stellate cells may re-gain a quiescent phenotype when implanted into the in vivo microenvironment or incorporated into multicellular 3D tissues comprising other liver cell types. Hepatic Stellate Cells are now available through Samsara Sciences.