Activated hepatic stellate cell (aHSC)

Activated hepatic stellate cells (aHSCs) represent the transdifferentiated, myofibroblast-like phenotype of quiescent hepatic stellate cells, which are the primary pericytes of the liver. In response to chronic liver injury—such as viral hepatitis, alcohol abuse, or metabolic dysfunction-associated steatohepatitis (MASH)—these cells undergo a complex activation process characterized by the loss of vitamin A droplets and the upregulation of alpha-smooth muscle actin (α-SMA) [Friedman SL, Physiol Rev, 2008]. Once activated, aHSCs become the principal source of excessive extracellular matrix (ECM) deposition, leading to the progressive scarring known as liver fibrosis and eventually cirrhosis [Tsuchida T, Nat Rev Gastroenterol Hepatol, 2017]. They also contribute to the inflammatory microenvironment by secreting pro-inflammatory cytokines and chemokines that recruit immune cells to the site of injury [Mederacke I, Nat Commun, 2013]. Therapeutic strategies targeting aHSCs focus on inhibiting their activation, promoting their reversion to a quiescent state, or inducing their apoptosis to halt or reverse fibrotic progression. Despite their central role in disease, targeting aHSCs remains a significant challenge in drug development because they are a complex cell type rather than a single molecular target, requiring precise delivery to avoid systemic toxicity.

Other names

Myofibroblast-like hepatic stellate cellActivated Ito cellPerisinusoidal cellLipocyteFat-storing cell

Suppression of myofibroblast transformation, inhibition of pro-fibrotic signaling pathways such as TGF-beta and PDGF, and induction of cellular senescence or apoptosis in the activated cell population.