Organizational Principles of the Liver

Grisham, Joe W.

doi:10.1002/9780470747919.ch1

Cited by 20 publications

(23 citation statements)

References 79 publications

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“…The liver is considered a part of this system, because it drains ∼1-2 l of blood/min, of which 75% is portal venous blood that has perfused the gut (36). Information regarding the immune cells that reside in the intrahepatic vascular bed is scarce and derived principally from studies performed in mice (2).…”

Section: Discussionmentioning

confidence: 99%

IL-7 Licenses Activation of Human Liver Intrasinusoidal Mucosal-Associated Invariant T Cells

Tang

Tan

et al. 2013

The Journal of Immunology

311

408

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Human mucosal-associated invariant T (MAIT) cells are a T cell population characterized by the expression of a semi-invariant TCR capable of recognizing bacterial products in the context of MR1. MAIT cells are enriched in the human liver, which is constantly exposed to bacterial products from the intestine. Whether this specific parenchymal localization influences their function remains unknown. We analyzed MAIT cells resident in the vascular bed of livers and showed that they represented the majority of T cells expressing NK markers and the dominant IL-17A+ T cell subset in the human liver sinusoids. In comparison with MAIT cells purified from peripheral blood, intrasinusoidal MAIT cells expressed markers of T cell activation; however, TCR-mediated cytokine production was equally suppressed in both circulating and intrasinusoidal MAIT cells. MAIT cells also expressed high levels of IL-7R, and we showed that IL-7, a cytokine produced by hepatocytes during inflammation, regulated TCR-mediated activation of MAIT cells, licensing them to dramatically increase Th1 cytokines and IL-17A production. Our quantitative and functional data indicate that MAIT cells are a specialized cell population highly adapted to exert their immune functions in the vascular network of the liver.

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Section: Discussionmentioning

confidence: 99%

IL-7 Licenses Activation of Human Liver Intrasinusoidal Mucosal-Associated Invariant T Cells

Tang

Tan

et al. 2013

The Journal of Immunology

311

408

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“…4), based on the classic hexagonal lobule of liver histology [26]. The central vein (CV), terminal portal vein (tPV) and pre-terminal portal vein (pre-tPV) were presented as cut channels along the edge of the lobule (Fig.…”

Section: Methodsmentioning

confidence: 99%

Multiscale computational model of fluid flow and matrix deformation in decellularized liver

Nishii

Reese

Moran

et al. 2016

Journal of the Mechanical Behavior of Biomedical Materials

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Currently little is known about the biomechanical environment in decellularized tissue. The goal of this research is to quantify the mechanical microenvironment in decellularized liver, for varying organ-scale perfusion conditions, using a combined experimental/computational approach. Needle-guided ultra-miniature pressure sensors were inserted into liver tissue to measure parenchymal fluid pressure ex-situ in portal vein-perfused native (n=5) and decellularized (n=7) ferret liver, for flow rates from 3–12 mL/min. Pressures were also recorded at the inlet near the portal vein cannula to estimate total vascular resistance of the specimens. Experimental results were fit to a multiscale computational model to simulate perfusion conditions inside native versus decellularized livers for four experimental flow rates. The multiscale model consists of two parts: an organ-scale electrical analog model of liver hemodynamics and a tissue-scale model that predicts pore fluid pressure, pore fluid velocity, and solid matrix stress and deformation throughout the 3D hepatic lobule. Distinct models were created for native versus decellularized liver. Results show that vascular resistance decreases by 82% as a result of decellularization. The hydraulic conductivity of the decellularized liver lobule, a measure of tissue permeability, was 5.6 times that of native liver. For the four flow rates studied, mean fluid pressures in the decellularized lobule were 0.6 to 2.4 mmHg, mean fluid velocities were 211 to 767 µm/s, and average solid matrix principal strains were 1.7 to 6.1%. In future this modeling platform can be used to guide the optimization of perfusion seeding and conditioning strategies for decellularized scaffolds in liver bioengineering.

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“…The liver receives blood supply from both the hepatic artery and the portal vein [1], and is composed by hepatocytes (that occupy almost 80% of total liver volume and perform the majority of liver functions), sinusoidal endothelial cells, Kupffer cells and hepatic stellate cells (HSC) [2]. This organ takes up nutrients, acting as store or provider to other organs, metabolizes a wide variety of nutrients and xenobiotics and serves as an excretory organ for bile pigments, cholesterol, bacterial products, and drugs [3,4]. In consequence, this organ is highly susceptible to the effects of toxins [5].…”

Section: Q2mentioning

confidence: 99%

Ellagic acid: Pharmacological activities and molecular mechanisms involved in liver protection

García-Niño

Zazueta

2015

Pharmacological Research

222

120

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Organizational Principles of the Liver

Cited by 20 publications

References 79 publications

IL-7 Licenses Activation of Human Liver Intrasinusoidal Mucosal-Associated Invariant T Cells

IL-7 Licenses Activation of Human Liver Intrasinusoidal Mucosal-Associated Invariant T Cells

Multiscale computational model of fluid flow and matrix deformation in decellularized liver

Ellagic acid: Pharmacological activities and molecular mechanisms involved in liver protection

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