Stellate cells are star-shaped cells with multiple extensions. These specialized cells are found in various parts of the body and perform diverse functions, depending on their location. Stellate cells possess a dual nature, playing beneficial roles in healthy tissues while also contributing to disease processes. Understanding their behavior offers insights into both normal bodily functions and the mechanisms of certain conditions.
Locations and Types of Stellate Cells
Stellate cells are present in several organs, with two types being extensively studied for their significant roles: hepatic stellate cells (HSCs) and pancreatic stellate cells (PSCs). Hepatic stellate cells reside in the liver’s perisinusoidal space, between liver cells and blood vessels. Pancreatic stellate cells are found in the exocrine regions of the pancreas, located in the peri-acinar spaces and also around small ducts and blood vessels. While star-shaped cells like astrocytes also exist in the central nervous system, scientific discussions about “stellate cells” in the context of organ scarring typically refer to HSCs and PSCs.
The Normal Role of Stellate Cells
In a healthy state, stellate cells remain quiescent, or inactive, acting as housekeepers within their organs. Hepatic stellate cells are the body’s primary storage site for vitamin A, storing 50–80% of the body’s total vitamin A within lipid droplets in their cytoplasm. These cells also contribute to maintaining liver homeostasis. Pancreatic stellate cells, in their quiescent state, maintain the normal structure and integrity of the pancreas by regulating the synthesis and degradation of extracellular matrix (ECM) proteins, ensuring a balanced turnover of the ECM.
Activation and Transformation in Disease
Stellate cells transform from their quiescent state to an activated, myofibroblast-like phenotype in response to tissue injury or chronic stress. This activation can be triggered by various factors, including toxins, chronic inflammation, or viral infections. During activation, hepatic stellate cells lose their lipid droplets and begin to express alpha-smooth muscle actin (α-SMA), a protein associated with muscle contraction. Pancreatic stellate cells similarly transform into myofibroblast-like cells, gaining contractile abilities and an increased growth of their endoplasmic reticulum. These activated cells proliferate, migrate to sites of injury, and acquire new problematic functions.
The Role of Stellate Cells in Fibrosis
The activated stellate cells become the primary drivers of fibrosis, a condition characterized by excessive scar tissue formation. They produce excessive extracellular matrix proteins, predominantly collagen type I and III, which accumulate in the tissue. This overproduction of collagen leads to the stiffening of the affected organ, impairing its normal function. In the liver, activated hepatic stellate cells are the main source of scar tissue that leads to liver cirrhosis, a severe condition where normal liver tissue is replaced by fibrous scars. Similarly, activated pancreatic stellate cells contribute to the dense, fibrous stroma seen in chronic pancreatitis and pancreatic cancer, significantly impacting the progression of these diseases.
Therapeutic Targeting of Stellate Cells
Given their central role in fibrosis, stellate cells are a key focus for developing new therapeutic strategies. Researchers are exploring various approaches to counteract their harmful effects. One strategy involves reverting activated stellate cells back to their quiescent state, potentially reversing the fibrotic process. Another approach aims to induce the programmed death, or apoptosis, of activated stellate cells while sparing healthy cells in the organ. Scientists are also investigating methods to directly block the ability of activated stellate cells to produce excessive collagen and other extracellular matrix components. These therapeutic avenues hold promise for mitigating organ damage caused by fibrosis.