Stellate cells

Abstract

Hepatic stellate cells (HSC) are located in the space of Disse in close contact with hepatocytes and sinusoidal endothelial cells. In human liver, HSC are disposed along the sinusoids with a nucleus-to-nucleus distance of 40∈μm, indicating that the sinusoids are equipped with HSC at certain fixed distances [1]. These observations suggest that, although the total number of HSC constitutes a small percentage of the total number of liver cells (approximately 5-8%), their spatial disposition and extension may be sufficient to cover the entire hepatic sinusoidal microcirculatory network. This cell type has received much attention in the past two decades, the reason being its potential involvement in the fibrogenic transformation of liver tissue following chronic injury. Because of their anatomical location, ultrastructural features, and similarities with pericytes regulating blood flow in other organs, HSC have been proposed to function as liver-specific pericytes. Branches of the autonomic nerve fibers coursing through the space of Disse come in contact with HSC [2], and the nerve endings containing substance P and vasoactive intestinal peptide have been demonstrated in the vicinity of HSC [3]. Other peculiar features that suggest a functional relationship between the autonomic nervous system and HSC are the expression of N-CAM, a typical central nervous system adhesion molecule detected in hepatic nerves, and the expression of glial fibrillary acidic protein (GFAP) are restricted, among liver cell types, to HSC [4]. These observations, while reinforcing a potential functional relationship between the autonomic nervous system and HSC, raise a current key issue concerning the origin of this cell type, previously considered to be of myogenic origin owing to the expression of desmin and smooth muscle α-actin (α-SMA). Along these lines, activated HSC express nestin, a class VI intermediate filament protein originally identified as a marker for neural stem cells [5]. Remark-ably, the expression of this cell marker appears to be restricted to HSC and pericytes of brain parenchyma vessels, among all organ-specific pericytes. Adding to the intriguing features of these cells,-quiescent stellate cells also express epimorphin, a mesenchymal morphogenic protein, which is increased after partial hepatectomy, coincident with a decline in stellate cell expression of α-SMA [6]. © 2010 Springer-Verlag Berlin Heidelberg.