During the past few decades, hepatic stellate cells have received much attention for their potential role in the pathogenesis of liver diseases. These cells are profibrogenic, act as antigen-presenting cells, and contribute to liver immunity. Various cell lines of hepatic stellate cells are now available, which help determine the molecular mechanisms that regulate their function. 

Hepatic stellate cells

The liver is a critical organ in the immune system. It is composed of hepatocytes, macrophages, and dendritic cells. It is the leading site for storing vitamin A, essential for average growth and reproduction. Most of the retinol in the body is stored as retinyl esters in lipid droplets within hepatic stellate cells. A large amount of retinoic acid is released during liver damage, which may mediate the immune response. Retinoic acid may also help in liver regeneration.

In addition to storing vitamin A, hepatic stellate cell function as profibrogenic cells. They initiate the synthesis of erythropoietin, a hematopoietic growth factor. They also trigger the synthesis of polypeptide mediators and extracellular matrix proteins. In addition, hepatic stellate cell expression of Toll-like receptors (TLRs) has been reported. In addition, HSCs are thought of as regulatory bystanders that modulate immune cell activity and intercellular communication.

Hepatic stellate cells are thought to be essential profibrogenic cells in the liver. They are resident in the perisinusoidal space of the Disse, a recess between the SECs and hepatocytes. In a normal human liver, HSCs are located at 3.6 to 6 cells per 100 hepatocytes.

These cells can transdifferentiate into collagen-producing myofibroblasts. In addition, they can promote hepatocellular carcinoma in immunocompetent mice. They also exhibit strong expression in the perinuclear region of the hepatocytes. In addition, they also show neurohumoral responsiveness. This is suggested to be an explanation for the heterogeneity of the hepatic stellate cell population.

Several studies have shown that hepatic stellate cells contribute to the development of hepatocellular carcinoma. In addition, they can also act as immunosuppressive cells. These cells can impair the function of dendritic cells. They also contribute to metastasis and tumor-induced immune suppression.

Hepatocellular carcinoma

During the development and progression of hepatocellular carcinoma (HCC), hepatic stellate cells (HSCs) play an essential role. They are critical interstitial cells in the tumor microenvironment (TME). They play a crucial role in early intrahepatic invasion and metastasis. HSCs also contribute to the development of fibrosis. However, the mechanism for their interaction with HCC cells remains unknown. Consequently, further elucidation of the functional mechanisms is essential for developing HCC therapy.

HSCs are activated by releasing extracellular vesicles (EVs) and miRNAs. EVs from cancer cells promotes invasion and metastasis through altered signal transduction pathways. They are also involved in drug resistance. They contribute to a positive feedback loop in HCC progression. In particular, they promote HCC cell proliferation by activating the AKT signaling pathway. In addition, they encourage hepatocarcinogenesis through the secretion of extracellular matrix proteins. They also contribute to immunosuppression and angiogenesis. They, therefore, promise therapeutic targets.

Hepatic Cells and Liver Fibrosis

Hepatic stellate cells (HSC) have been identified as the major cell type involved in liver fibrosis. These cells are proliferative myofibroblasts with a cell-cell interaction that has important implications for liver pathophysiology. There are two morphologically distinct forms of HSC: quiescent and activated. They differ in their developmental biology and expression of mesenchymal markers. They are also distinguished by the presence of intracytoplasmic lipid droplets. These are important for their role in the storage of vitamin A.

In addition to its primary function as an organ recycling center, the liver is a major host for innate and adaptive immunity. The cells of the liver are responsible for detecting and responding to altered tissue integrity. They are key players in the initiation of inflammatory responses in various disease settings. They can also promote hepatocellular carcinoma and other malignancies. They are capable of transdifferentiating into collagen-producing myofibroblasts. They are also involved in the apoptotic body engulfment of necrotic hepatocytes. In addition, their interactions with macrophages play an essential role in the pathogenesis of chronic liver diseases.

Hepatic stellate cell interaction with macrophages is one of the most important features of the microenvironment of chronic liver diseases. The effects of this interaction on hepatic fibrosis have been studied extensively. 

The physiology of hepatic stellate cells is complex. They interact with numerous liver cells, including macrophages, dendritic cells, and sinusoidal endothelial cells. They are also affected by autophagy, autoantibody production, and endoplasmic reticulum stress. In addition, they are involved in mediating Hedgehog signaling. In addition, they produce various interleukins. There are approximately forty ILs have been identified as being associated with HSC activation. The majority of these ILs are required for proper immune system function. Some of these ILs have been linked to the ability of HSC to promote tumor angiogenesis.

Several studies have demonstrated that hepatic stellate cells are important in the pathogenesis of liver injury. Some of these effects are thought to be mediated by hematopoietic stem cell-derived cells that give rise to activated hepatic stellate cells during liver injury. These hematopoietic setlls m ceappear to contribute to liver injury by forming a tumor-associated milieu, which enhances the responsiveness of tumor cells to soluble factors.

Hepatic stellate fusion occurs in several instances, especially in bone marrow-derived cells. These cells fuse with hepatocytes and Purkinje neurons. They may also have an important role in liver regeneration.