06 May 2013

Liver-on-a-chip in Korean

Three-dimensional microcapillary liver

ChemPort.Ru based on the materials of Lab on a Chip: Seung-A Lee et al.,
Spheroid-based three-dimensional liver-on-a-chip to investigate hepatocyte-hepatic stellate cell interactions and flow effects.

Researchers from South Korea have developed a three-dimensional model of the liver that can reproduce the features of the cellular signaling system in this organ. Such a liver model in the future may stop the practice of using experimental animals to study the interaction of new drugs with liver cells.

The liver consists of two types of cells. 80% of the cells of this organ are hepatocytes, and the remaining 20% are nonparenchymatous cells, among which there are stellate liver cells – lipocytes, hepatic stellate cells (HSC). When the liver is damaged, lipocytes work together with hepatocytes, playing a huge role in the regeneration of liver tissue. However, to date, the specifics of the interaction between lipocytes and hepatocytes are not yet clear, although there are ideas that direct contact of cells with each other and their "communication" at a distance, also known as paracrine signaling, plays a role in this. Despite the existing artificial models of the liver, no studies have been conducted on the systematic study of paracrine signaling.

Design concept (top) and mechanism of action (bottom) of the new device
(picture from an article in Lab on a Chip).

A group of researchers led by SangHoon Lee from the University of Korea have developed a new three-dimensional spherical cell culture system that can effectively simulate the three-dimensional placement of natural liver cells. To obtain homogeneous three-dimensional structures, the new system is equipped with concave micro-rings. At the same time, lipocytes were cultured in some wells, and hepatocytes in others to exclude the possibility of direct cellular contact. Communication between different types of cells was carried out by microcapillary tubes, and the osmotic pump allows continuous monitoring in the supply of nutrients and waste disposal to the system.

The osmotic pump also allows you to control the flow rate of the nutrient flow. This circumstance allows the microcapillary liver to more accurately simulate the work of living tissue and allows scientists to investigate how the flow rate affects paracrine interactions. Lee explains that his group has developed a device that integrates all liver functions within a single microcapillary system, compact enough to work for a long time without complex peripheral devices.

When testing the microcapillary liver, it was found that short-acting paracrine interactions of lipocytes and hepatocytes affect liver function and increase the efficiency of its functioning to a greater extent than direct contacts of cells of different types with each other. The optimal flow rate was also selected, at which the aggregation of cells into a spherical shape occurs, and this effective shape remains unchanged for a long time.

Gretchen Mahler, an expert in three-dimensional modeling of biological tissues using microcapillary devices, notes that the microcapillary liver is a promising device for high-performance screening of drugs. Mahler emphasizes that the ability to cultivate cells in a three-dimensional direction, while maintaining specific liver functions for a relatively long period with minimal costs, is a step forward compared to currently existing methods.

Portal "Eternal youth" http://vechnayamolodost.ru06.05.2013

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