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A Microfluidically Perfused Three Dimensional Human Liver Model

A Microfluidically Perfused Three Dimensional Human Liver Model

Knut Rennert, Sandra Steinborn, Marko Gröger, Birgit Ungerböck, Anne-Marie Jank, Josef Ehgartner, Sandor Nietzsche, Julia Dinger, Michael Kiehntopf, Harald Funke, Frank T Peters, Amelie Lupp, Claudia Gärtner, etc.

Biomaterials. 2015 Dec;71:119-131.

PMID: 26322723

Abstract:

Within the liver, non-parenchymal cells (NPCs) are critically involved in the regulation of hepatocyte polarization and maintenance of metabolic function. We here report the establishment of a liver organoid that integrates NPCs in a vascular layer composed of endothelial cells and tissue macrophages and a hepatic layer comprising stellate cells co-cultured with hepatocytes. The three-dimensional liver organoid is embedded in a microfluidically perfused biochip that enables sufficient nutrition supply and resembles morphological aspects of the human liver sinusoid. It utilizes a suspended membrane as a cell substrate mimicking the space of Disse. Luminescence-based sensor spots were integrated into the chip to allow online measurement of cellular oxygen consumption. Application of microfluidic flow induces defined expression of ZO-1, transferrin, ASGPR-1 along with an increased expression of MRP-2 transporter protein within the liver organoids. Moreover, perfusion was accompanied by an increased hepatobiliary secretion of 5(6)-carboxy-2',7'-dichlorofluorescein and an enhanced formation of hepatocyte microvilli. From this we conclude that the perfused liver organoid shares relevant morphological and functional characteristics with the human liver and represents a new in vitro research tool to study human hepatocellular physiology at the cellular level under conditions close to the physiological situation.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP111843788	5(6)-Carboxy-2′,7′-dichlorofluorescein		111843-78-8	Price
AP76540	2′,7′-Dichlorofluorescein		76-54-0	Price

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