Hepatic Stellate Cell

Hepatic Stellate Cells : short history

kupffer.jpgStellate cells were discovered serendipitously by Karl von Kupffer in 1876 when he was investigating the micro-anatomy of the hepatic nervous system. He tried to stain the nerves by a goldchloride impregnation method, but instead stained star-shaped cells that he called "sternzellen". For nearly 100 years the cells remained enigmatic until Kenjiro Wake, Professor of Anatomy at the University of Tokyo, Japan, summarized all the available information and defined the stellate cell as a cell type in its own right.

Hepatic stellate cells have been studied intensively since 1975. There is overwhelming evidence that these cells play a prominent role in development of hepatic fibrosis and cirrhosis (endstage of fibrotic liver disease). In Belgium, approximately 1500 people per year die as a result of chronic liver disease that has developed into cirrhosis. In the different countries of the European Union, chronic liver disease is between the 4th and 8th cause of death.

Since 1998, pancreatic stellate cells have come into the picture. The available evidence indicates that pancreatic stellate cells play a cardinal role in pancreatic fibrosis which develops as a result of chronic pancreatitis or of diabetes type II.

Stellate cells have also been found in many other organs as is summarized in the table underneath.

Organ system

Organ/tissue

GI tract

salivary gland, oesophagus, gastric fundus, duodenum, liver, pancreas, ileum, rectum

Eye

lacrimal gland

Respiratory tract

vocal fold, lung

Urinary tract

kidney, prostate

Endocrine system

adrenal, pituitary

Female reproductive system

uterus

Male reproductive system

ductus deferens

Lymphoid organs

spleen, lymphe node, tonsil

Hematopoietic system

bone marrow

Exception made for the liver and the pancreas, stellate cells in other organs have not been thoroughly studied. However, these cells may be involved in important pathologies such as emphysema in the lung, interstitial and glomerular fibrosis in the kidney, inflammatory bowel diseases and Sjögren´s syndrome in the salivary glands. As is the case for cirrhosis and pancreatic fibrosis, the above diseases are characterized by development of significant amounts of fibrotic tissue that replaces functional tissue of the affected organ.

In primary as well as in metastatic liver tumors, activated stellate cells act as stromal cells. These stromal cells produce extracellular matrix required for neo-angiogenesis, allowing the tumor to expand. These stromal cells also produce matrix metalloproteinases allowing tumor cells to metastazise.

Besides the classical functions that are attributed to hepatic stellate cells (vitamin A storage, ECM synthesis, contraction, secretion of growth factors and cytokines, neural signal propagation), it appears that a subpopulation of these cells plays a role in formation of the progenitor cell niches.