The Space of Disse: The Liver Hub in Health and Disease

Abstract

Since it was first described by the German anatomist and histologist, Joseph Hugo Vincenz Disse, the structure and functions of the space of Disse, a thin perisinusoidal area between the endothelial cells and hepatocytes filled with blood plasma, have acquired great importance in liver disease. The space of Disse is home for the hepatic stellate cells (HSCs), the major fibrogenic players in the liver. Quiescent HSCs (qHSCs) store vitamin A, and upon activation they lose their retinol reservoir and become activated. Activated HSCs (aHSCs) are responsible for secretion of extracellular matrix (ECM) into the space of Disse. This early event in hepatic injury is accompanied by loss of the pores—known as fenestrations—of the endothelial cells, triggering loss of balance between the blood flow and the hepatocyte, and underlies the link between fibrosis and organ dysfunction. If the imbalance persists, the expansion of the fibrotic scar followed by the vascularized septae leads to cirrhosis and/or end-stage hepatocellular carcinoma (HCC). Thus, researchers have been focused on finding therapeutic targets that reduce fibrosis. The space of Disse provides the perfect microenvironment for the stem cells niche in the liver and the interchange of nutrients between cells. In the present review article, we focused on the space of Disse, its components and its leading role in liver disease development.

Methotrexate-Induced Liver Injury Is Associated with Oxidative Stress, Impaired Mitochondrial Respiration, and Endoplasmic Reticulum Stress In Vitro

“…In addition to the moderate but consistent toxicity towards HepaRG, we investigated the effects of MTX on the hepatic stellate cell. Progression of fibrosis is closely linked to the activation of HSCs and subsequent deposition of ECM into the space of Disse, leading to increased liver stiffness and portal hypertension [ 66 ]. Several pathways are involved in the activation of HSCs, including oxidative stress, ER stress, and activation of the A 2A receptor by adenosine [ 67 , 68 ].…”

Chemical, Molecular, and Single-nucleus Analysis Reveal Chondroitin Sulfate Proteoglycan Aberrancy in Fibrolamellar Carcinoma

“…The expression and secretion of VCAN from activated stellate cells is a normal response to liver injury (60)(61)(62)(63). The data generated in this study suggest that FLC cells upregulate CSGALNACT and VCAN in a DP-dependent manner and begin secreting CS-VCAN PG into the extracellular matrix.…”

Chemical, molecular, and single cell analysis reveal chondroitin sulfate proteoglycan aberrancy in fibrolamellar carcinoma

“…The expression and secretion of VCAN from activated stellate cells is a normal response to liver injury (48)(49)(50)(51) . The data generated in this study suggest that FLC cells upregulate CSGALNACT1 and VCAN in a DPdependent manner and begin secreting CS-VCAN proteoglycan into the extracellular matrix.…”