Hepatic Stellate Cells: A delicate balance

Hepatic stellate cells have recently gained a great deal of attention regarding their contribution to the progression of diseases such as liver fibrosis, non-alcoholic steatohepatitis (NASH), and hepatocellular carcinoma. Hepatic stellate cells are mesenchymal cells that are located between sinusoidal endothelial cells and hepatocytes in the space of Disse or perisinusoidal space and represent about 5-10% of cells in the liver. Hepatic stellate cells play a critical role in liver homeostasis and perform a diverse set of functions, some of which are poorly understood. In a normal healthy liver, stellate cells are quiescent and store vitamin A droplets.  Additionally, stellate cells are involved in vasoregulation, monitoring extracellular matrix deposition, and the production of factors that stimulate hepatocyte regeneration.

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In response to liver damage, stellate cells receive signals from hepatocytes, hepatic sinusoidal endothelial cells, and immune cells to activate.  Once given the signal to activate, hepatic stellate cells transdifferentiate into myofibroblasts and produce extracellular matrix (ECM), such as collagen type I and III. At this point, the activated cells lose the vitamin A lipid droplets and begin to express α-smooth muscle actin. The deposition of ECM by the stellate cells creates a scar, which helps to reduce further liver damage. If liver damage continues to occur, stellate cells will remain activated and continue to produce ECM promoting liver fibrosis. Paradoxically, while stellate cells play a key role in liver repair and regeneration, they also promote the progression of liver disease by their continuous deposition of ECM.

Recent studies have begun to examine transcriptional regulation of hepatic stellate cells in NASH and the role transcription factors play in activation of stellate cells. Other studies indicate that cancer associated fibroblasts, most likely derived from hepatic stellate cells, communicate with cancer cells to promote tumor growth and angiogenesis. The intricacies of hepatic stellate cell activation are just beginning to be elucidated through epigenetic regulation research.

Due to the complex nature of hepatic stellate cells and their importance in liver disease, further studies are needed to elucidate the cellular and molecular mechanisms of these cells. Understanding the role of hepatic stellate cells in liver fibrosis will help drive the development of novel therapeutics for liver disease.  At ScienCell Research Laboratories, we offer normal human, rat, and mouse primary hepatic stellate cells to researchers studying diseases such as liver fibrosis, NASH, alcoholic liver disease, and hepatocellular carcinoma. We also offer gene expression analysis kits, known as GeneQuery, for exploring hepatic stellate cell biology.

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