History, Heterogeneity, Developmental Biology, and Functions of Quiescent Hepatic Stellate Cells

Abstract

In 1876, von Kupffer described liver Sternzellen (star-shaped cells). The functions of these cells remained enigmatic for 75 years until Ito observed lipid-containing perisinusoidal cells in human liver. In 1971, Wake demonstrated that the Sternzellen of von Kupffer and the fat-storing cells described by Ito were identical. Wake also established that these cells were important sites of vitamin A storage. Soon thereafter, Kent and Popper demonstrated that the stellate cells were intimately linked to the pathogenesis of hepatic fibrosis. Since then, these cells have been studied in detail. Quiescent stellate cells represent 5-8% of the total number of liver cells. They play a cardinal role in storage and controlled release of retinoids. They control extracellular matrix (ECM) turnover in the space of Disse by secreting the correct amounts of a limited number of ECM molecules, and by releasing matrix metalloproteinases and their inhibitors. By virtue of their long cytoplasmic processes, quiescent stellate cells presumably contribute to the control of blood flow through the sinusoidal capillaries. They are important sources of paracrine, autocrine, juxtacrine, and chemoattractant factors that maintain homeostasis in the microenvironment of the hepatic sinusoid.Objectives: Upon completion of this article, the reader should be able to (1) describe the morphology and intrahepatic localization of stellate cells, (2) discuss the pros and cons of the markers that are currently used to stain stellate cells in liver tissue, (3) compare stellate cells to other hepatic fibrogenic cells, (4) understand the concept of extrahepatic stellate cells, and (5) list the major physiological functions of hepatic stellate cells. Accreditation: Tufts University School of Medicine is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. TUSM takes full responsibility for the content, quality, and scientific integrity of this continuing education activity. Credit: Tufts University School of Medicine designates this education activity for a maximum of 1.0 hour credit toward the AMA Physicians Recognition Award in category one. Each physician should claim only those hours that he/she actually spent in the educational activity.

The niche of stellate cells within rat liver #

“…2 Controversies exist about the embryonic origin of HSCs, because they express proteins of all three germ layers. 3 Bone marrow stem cells are able to generate cells of all germ layers, and it was suggested that the bone marrow might be a source of stellate cells in adult vertebrate liver. 4,5 This indicates a mesodermal origin of stellate cells, which was confirmed by a very recent study.…”

Apoptotic Body Engulfment by a Human Stellate Cell Line Is Profibrogenic

“…Under basal conditions, hepatic stellate cells are in a quiescent state and function to store retinoids within the liver (Blomhoff et al, 1990;Geerts, 2001). However, upon activation, these cells undergo transformation, assuming a myofibroblast morphology and expressing smooth muscle actin (Ramadori et al, 1990;Schmitt-Graff et al, 1991).…”

Remodeling of hepatic vascular changes after specific chemotherapy of schistosomal periportal fibrosis

“…Such observations were registered at a time when the concept about the irreversibility of hepatic fibrosis was taken for granted. Nowadays, such possibility is admitted while the cases of successful liver fibrosis rever- sion are being published (Geerts 2001, Desmet & Roskams 2004, which included even cases of far advanced cirrhosis (Arthur 2002, Massarrat et al 2004.…”