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This research was funded by Atraccion de Talento de la Comunidad Autonoma 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 Ramon y Cajal Researcher RYC-2015-17438 and RYC-2014-15242, respectively. F.J.C. is a Gilead LiverResearch 2018. The research group belongs to the validated Research Groups Ref. 970935 "Liver Pathophysiology",920631 "Lymphocyte immunobiology", 920361 "Inmunogenetica e inmunologia de las mucosas" and IBL-6(imas12-associated).

Impact on the Sustainable Development Goals (SDGs)

Analysis of institutional authors

Fernandez-Iglesias, AnabelAuthorGracia-Sancho, JordiAuthor

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Review

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

Publicated to:Livers. 1 (1): 3-26 - 2021-03-01 1(1), DOI: 10.3390/livers1010002

Authors: Sanz-Garcia, Carlos; Fernandez-Iglesias, Anabel; Gracia-Sancho, Jordi; Arraez-Aybar, Luis Alfonso; Nevzorova, Yulia A; Cubero, Francisco Javier

Affiliations

12 Octubre Hlth Res Inst IMAS12, Madrid 28040, Spain - Author
Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid 28029, Spain - Author
IDIBAPS, Liver Vasc Biol Res Grp, Barcelona 08036, Spain - Author
Univ Bern, Dept Biomed Res, Hepatol, CH-3012 Bern, Switzerland - Author
Univ Complutense Madrid, Sch Med, Dept Anat & Embriol, Madrid 28040, Spain - Author
Univ Complutense Madrid, Sch Med, Dept Immunol Ophthalmol & ENT, Madrid 28040, Spain - Author
Univ Hosp RWTH Aachen, Dept Internal Med 3, D-52074 Aachen, Germany - Author
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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.

Keywords

Chronic liver diseaseExtracellular matrix (ecmExtracellular matrix (ecm)FibrosisGood health and well-beingHedgehog pathwayHepatic stellate cellsHepatic stellate cells (hscs)Killer t-cellsKupffer cellsKupffer cells (kcs)Liver sinusoidal endothelial cells (lsecs)Natural-killerNonalcoholic steatohepatitisPortal-hypertensioSinusoidal endothelial-cellsTgf-betaToll-like receptors

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

From a relative perspective, and based on the normalized impact indicator calculated from the Field Citation Ratio (FCR) of the Dimensions source, it yields a value of: 6.09, which indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: Dimensions Jul 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-07-02, the following number of citations:

  • WoS: 24
  • Scopus: 26
  • Open Alex: 34

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-07-02:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 109.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 109 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 1.85.
  • The number of mentions on the social network X (formerly Twitter): 3 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.
Continuing with the social impact of the work, it is important to emphasize that, due to its content, it can be assigned to the area of interest of ODS 3 - Good Health And Well-being, with a probability of 65% according to the mBERT algorithm developed by Aurora University.

Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: Germany; Switzerland.