Publication: The Space of Disse: The Liver Hub in Health and Disease
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2021
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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.
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This research was funded by Atracción de Talento de la Comunidad Autónoma de Madrid, 2019-T1/BMD-13313; and the MINECO Retos SAF2016-78711 and SAF2017-87919-R, EXOHEP-CM S2017/BMD-3727, NanoLiver-CM Y2018/NMT-4949, ERAB Ref. EA 18/14, AMMF 2018/117, UCM-25-2019, the German Research Foundation (SFB/TRR57/P04, SFB 1382-403224013/A02 and DFG NE 2128/2-1), and COST Action CA17112. Y.A.N. and F.J.C. are Ramón y Cajal Researcher RYC-2015-17438 and RYC-2014-15242, respectively. F.J.C. is a Gilead Liver Research 2018. The research group belongs to the validated Research Groups Ref. 970935 “Liver Pathophysiology”, 920631 “Lymphocyte immunobiology”, 920361 “Inmunogenética e inmunología de las mucosas” and IBL-6 (imas12-associated).